In this file, we presented the results from analyses of exposures against computed epigenetic age accelerations (EAA) calculated using DNA methylation data by different methods. For each exposure, we conducted both primary analyses (likelihood ratio tests and generalized estimating equations (GEE), adjusted for confounders) and sensitivity analyses (likelihood ratio tests and/or generalized estimating equations (GEE) limited to certain fuel users, not adjusted for confounders). In addition to what’s included in the analysis plan, we also analyzed ambient and urinary exposures.

1.1. Description of study population

There are 129 visits with corresponding epigenetic ages available among 106 female subjects. For these 106 subjects, 83 have been visited once and 23 have been visited twice.

The following tables summarize all the information of the first visit of these 106 subjects.

Baseline characteristics (confounders)

Overall
(N=106)
Age
Mean (SD) 56.2 (15.0)
Median (IQR) 58.0 (24.8)
BMI
Mean (SD) 22.0 (3.46)
Median (IQR) 21.7 (4.46)
factor(county)
Fuyuan 53 (50.0%)
Xuanwe 53 (50.0%)
factor(ses)
0 53 (50.0%)
1 53 (50.0%)
factor(edu)
1 72 (67.9%)
2 17 (16.0%)
3 13 (12.3%)
4 4 (3.8%)

Epigenetic ages

Overall
(N=106)
DNAmAge
Mean (SD) 56.3 (13.5)
Median (IQR) 57.6 (22.0)
DNAmAgeHannum
Mean (SD) 59.0 (14.4)
Median (IQR) 59.9 (23.7)
DNAmPhenoAge
Mean (SD) 54.7 (14.0)
Median (IQR) 54.8 (21.6)
DNAmAgeSkinBloodClock
Mean (SD) 55.8 (13.2)
Median (IQR) 57.6 (23.5)
DNAmGrimAge
Mean (SD) 55.3 (11.8)
Median (IQR) 57.2 (19.4)
DNAmTL
Mean (SD) 6.84 (0.329)
Median (IQR) 6.85 (0.461)

Epigenetic ages accelarations

Overall
(N=106)
AgeAccelerationResidual
Mean (SD) 0.182 (4.62)
Median (IQR) 0.213 (5.90)
AgeAccelerationResidualHannum
Mean (SD) -0.435 (4.06)
Median (IQR) -0.432 (4.79)
AgeAccelPheno
Mean (SD) -0.746 (4.45)
Median (IQR) -1.06 (5.61)
DNAmAgeSkinBloodClockAdjAge
Mean (SD) -0.000985 (3.43)
Median (IQR) 0.380 (3.58)
AgeAccelGrim
Mean (SD) -0.320 (2.96)
Median (IQR) -0.913 (3.27)
DNAmTLAdjAge
Mean (SD) 0.0307 (0.182)
Median (IQR) 0.0347 (0.238)
IEAA
Mean (SD) 0.0900 (4.34)
Median (IQR) 0.303 (5.90)
EEAA
Mean (SD) -0.534 (5.24)
Median (IQR) -0.425 (6.83)

Fuel/stove type exposures

Overall
(N=106)
factor(curFuel)
Other 18 (17.0%)
Smoky 72 (67.9%)
Missing 16 (15.1%)
factor(brthFuel)
Other 53 (50.0%)
Smoky 40 (37.7%)
Missing 13 (12.3%)
factor(cumFuel)
Other 64 (60.4%)
Smoky 32 (30.2%)
Missing 10 (9.4%)
factor(curStove)
Firepit_and_unventilated 16 (15.1%)
Mix 14 (13.2%)
Portable_stove 16 (15.1%)
Ventilated 44 (41.5%)
Missing 16 (15.1%)

5MC exposures

Overall
(N=106)
cur_5mc
Mean (SD) 8.13 (4.14)
Median (IQR) 7.61 (4.48)
Missing 2 (1.9%)
cum_5mc
Mean (SD) 266 (149)
Median (IQR) 236 (194)
Missing 2 (1.9%)
bir_5mc
Mean (SD) 5.14 (2.81)
Median (IQR) 4.73 (5.23)
Missing 2 (1.9%)
cur_5mc_measured
Mean (SD) 14.4 (42.2)
Median (IQR) 6.39 (5.80)
Missing 65 (61.3%)
## [1] "Pearson pair-wise correlation:"
##                    cur_5mc   cum_5mc     bir_5mc cur_5mc_measured
## cur_5mc          1.0000000 0.7055284  0.70960439       0.10311689
## cum_5mc          0.7055284 1.0000000  0.84246687       0.17631136
## bir_5mc          0.7096044 0.8424669  1.00000000      -0.04507814
## cur_5mc_measured 0.1031169 0.1763114 -0.04507814       1.00000000
## [1] "Spearman pair-wise correlation:"
##                    cur_5mc   cum_5mc   bir_5mc cur_5mc_measured
## cur_5mc          1.0000000 0.6580617 0.6721831        0.4434641
## cum_5mc          0.6580617 1.0000000 0.8313456        0.3335835
## bir_5mc          0.6721831 0.8313456 1.0000000        0.2297288
## cur_5mc_measured 0.4434641 0.3335835 0.2297288        1.0000000

Cluster-based exposures

clusCUR6

Clusters based on model-based exposure estimates at or shortly before the visit

Overall
(N=106)
CUR6_BC_PAH6
Mean (SD) 0.219 (0.960)
Median (IQR) 0.787 (1.20)
Missing 2 (1.9%)
CUR6_PAH31
Mean (SD) 0.191 (0.909)
Median (IQR) 0.403 (1.02)
Missing 2 (1.9%)
CUR6_NkF
Mean (SD) -0.0644 (1.09)
Median (IQR) -0.330 (1.34)
Missing 2 (1.9%)
CUR6_PM_RET
Mean (SD) -0.0117 (0.988)
Median (IQR) -0.291 (0.924)
Missing 2 (1.9%)
CUR6_NO2
Mean (SD) 0.0756 (1.01)
Median (IQR) -0.0205 (1.15)
Missing 2 (1.9%)
CUR6_SO2
Mean (SD) -0.182 (0.883)
Median (IQR) -0.298 (1.03)
Missing 2 (1.9%)

clusCHLD5

Clusters based on model-based exposure estimates accrued before age 18

Overall
(N=106)
CHLD5_X7
Mean (SD) -0.0658 (0.928)
Median (IQR) 0.0805 (0.953)
Missing 2 (1.9%)
CHLD5_X33
Mean (SD) 0.126 (0.998)
Median (IQR) -0.0315 (1.66)
Missing 2 (1.9%)
CHLD5_NkF
Mean (SD) -0.107 (1.10)
Median (IQR) -0.226 (1.51)
Missing 2 (1.9%)
CHLD5_NO2
Mean (SD) 0.130 (1.11)
Median (IQR) 0.214 (1.29)
Missing 2 (1.9%)
CHLD5_SO2
Mean (SD) -0.0538 (0.914)
Median (IQR) 0.324 (1.44)
Missing 2 (1.9%)

clusCUM6

Clusters based on model-based lifetime exposure estimates

Overall
(N=106)
CUM6_BC_NO2_PM
Mean (SD) 0.0308 (1.05)
Median (IQR) 0.166 (1.73)
Missing 2 (1.9%)
CUM6_PAH36
Mean (SD) 0.139 (0.979)
Median (IQR) 0.145 (1.63)
Missing 2 (1.9%)
CUM6_DlP
Mean (SD) -0.202 (1.03)
Median (IQR) -0.460 (1.76)
Missing 2 (1.9%)
CUM6_NkF
Mean (SD) -0.0565 (1.09)
Median (IQR) -0.162 (1.33)
Missing 2 (1.9%)
CUM6_RET
Mean (SD) -0.160 (1.03)
Median (IQR) -0.256 (1.15)
Missing 2 (1.9%)
CUM6_SO2
Mean (SD) -0.167 (0.950)
Median (IQR) -0.0634 (1.54)
Missing 2 (1.9%)

clusMEAS6

Clusters based on pollutant measurements

Overall
(N=106)
MEAS6_BC_PM_RET
Mean (SD) 0.000108 (1.01)
Median [Min, Max] 0.0508 [-2.22, 2.71]
Missing 57 (53.8%)
MEAS6_X31
Mean (SD) 0.0178 (1.03)
Median [Min, Max] 0.167 [-2.19, 2.41]
Missing 57 (53.8%)
MEAS6_X5
Mean (SD) 0.00997 (0.993)
Median [Min, Max] -0.104 [-1.44, 1.78]
Missing 57 (53.8%)
MEAS6_DlP
Mean (SD) -0.0237 (0.990)
Median [Min, Max] -0.639 [-1.02, 1.76]
Missing 57 (53.8%)
MEAS6_NkF
Mean (SD) 0.0452 (1.04)
Median [Min, Max] -0.499 [-1.20, 1.89]
Missing 57 (53.8%)
MEAS6_NO2_SO2
Mean (SD) 0.0311 (1.03)
Median [Min, Max] -0.118 [-1.61, 2.14]
Missing 57 (53.8%)

clusURI5

Clusters based on urinary biomarkers

Overall
(N=106)
URI5_NAP_1M_2M
Mean (SD) 0.0125 (0.967)
Median (IQR) 0.0710 (1.19)
Missing 13 (12.3%)
URI5_ACE
Mean (SD) -0.117 (0.989)
Median (IQR) -0.124 (1.34)
Missing 13 (12.3%)
URI5_FLU_PHE
Mean (SD) -0.0423 (0.955)
Median (IQR) 0.0580 (1.25)
Missing 13 (12.3%)
URI5_PYR
Mean (SD) -0.0557 (0.940)
Median (IQR) 0.0668 (0.841)
Missing 13 (12.3%)
URI5_CHR
Mean (SD) -0.0238 (1.03)
Median (IQR) -0.0345 (0.958)
Missing 13 (12.3%)

Ambient exposures

Overall
(N=106)
bap_air
Mean (SD) 66.3 (90.5)
Median (IQR) 39.5 (55.9)
Missing 3 (2.8%)
pm25_air
Mean (SD) 205 (188)
Median (IQR) 144 (133)
ANY_air
Mean (SD) 908 (1540)
Median (IQR) 486 (651)
Missing 33 (31.1%)
BPE_air
Mean (SD) 69.2 (93.1)
Median (IQR) 40.8 (51.7)
Missing 3 (2.8%)
BaA_air
Mean (SD) 91.3 (153)
Median (IQR) 43.7 (76.8)
Missing 3 (2.8%)
BbF_air
Mean (SD) 110 (151)
Median (IQR) 64.7 (92.2)
Missing 3 (2.8%)
BkF_air
Mean (SD) 23.5 (33.2)
Median (IQR) 13.2 (19.5)
Missing 3 (2.8%)
CHR_air
Mean (SD) 88.0 (141)
Median (IQR) 48.6 (74.5)
Missing 3 (2.8%)
DBA_air
Mean (SD) 23.1 (35.9)
Median (IQR) 11.0 (22.4)
Missing 3 (2.8%)
FLT_air
Mean (SD) 65.2 (146)
Median (IQR) 17.5 (41.0)
Missing 3 (2.8%)
FLU_air
Mean (SD) 441 (691)
Median (IQR) 250 (260)
Missing 33 (31.1%)
IPY_air
Mean (SD) 40.9 (49.7)
Median (IQR) 27.1 (33.5)
Missing 3 (2.8%)
NAP_air
Mean (SD) 5340 (8070)
Median (IQR) 3020 (3540)
Missing 33 (31.1%)
PHE_air
Mean (SD) 675 (1080)
Median (IQR) 351 (533)
Missing 33 (31.1%)
PYR_air
Mean (SD) 71.3 (149)
Median (IQR) 21.3 (50.6)
Missing 3 (2.8%)

Urinary biomarkers

Overall
(N=106)
Benzanthracene_Chrysene_urine
Mean (SD) 0.976 (3.49)
Median (IQR) 0.389 (0.465)
Missing 2 (1.9%)
Naphthalene_urine
Mean (SD) 247 (755)
Median (IQR) 113 (112)
Methylnaphthalene_2_urine
Mean (SD) 48.7 (64.7)
Median (IQR) 29.8 (29.4)
Missing 8 (7.5%)
Methylnaphthalene_1_urine
Mean (SD) 21.0 (26.4)
Median (IQR) 12.0 (18.7)
Missing 3 (2.8%)
Acenaphthene_urine
Mean (SD) 7.76 (11.4)
Median (IQR) 3.34 (5.84)
Phenanthrene_Anthracene_urine
Mean (SD) 216 (296)
Median (IQR) 116 (191)
Fluoranthene_urine
Mean (SD) 21.8 (25.1)
Median (IQR) 16.5 (17.5)
Pyrene_urine
Mean (SD) 0.744 (0.622)
Median (IQR) 0.552 (0.423)
Missing 15 (14.2%)

1.2. EAA ~ confounders

## For AgeAccelerationResidual :[1] "Fitting with 129 observations."
##              coefficient    std ci_lower ci_upper  p_val sig_level
## (Intercept)      -0.2555 4.8412  -9.7443   9.2334 0.9579    > 0.05
## Age               0.0164 0.0416  -0.0651   0.0979 0.6940    > 0.05
## countyXuanwe     -0.3183 0.8670  -2.0175   1.3810 0.7135    > 0.05
## BMI              -0.0820 0.1092  -0.2961   0.1321 0.4528    > 0.05
## ses               1.9126 1.2040  -0.4472   4.2724 0.1122    > 0.05
## edu               0.4074 0.5870  -0.7431   1.5580 0.4876    > 0.05
## For AgeAccelerationResidualHannum :[1] "Fitting with 129 observations."
##              coefficient    std ci_lower ci_upper  p_val sig_level
## (Intercept)      -4.0613 4.1892 -12.2720   4.1495 0.3323    > 0.05
## Age               0.0447 0.0389  -0.0316   0.1209 0.2508    > 0.05
## countyXuanwe      0.4064 0.7888  -1.1396   1.9523 0.6064    > 0.05
## BMI               0.0047 0.0903  -0.1722   0.1817 0.9584    > 0.05
## ses              -0.1213 1.2013  -2.4758   2.2332 0.9196    > 0.05
## edu               0.6429 0.5143  -0.3652   1.6509 0.2113    > 0.05
## For AgeAccelPheno :[1] "Fitting with 129 observations."
##              coefficient    std ci_lower ci_upper  p_val sig_level
## (Intercept)      -2.6519 3.9910 -10.4742   5.1704 0.5064    > 0.05
## Age               0.0252 0.0403  -0.0537   0.1042 0.5315    > 0.05
## countyXuanwe     -0.4712 0.8431  -2.1237   1.1813 0.5763    > 0.05
## BMI               0.0553 0.0890  -0.1191   0.2298 0.5341    > 0.05
## ses              -0.2758 1.0826  -2.3976   1.8461 0.7989    > 0.05
## edu              -0.0725 0.5041  -1.0606   0.9155 0.8856    > 0.05
## For DNAmAgeSkinBloodClockAdjAge :[1] "Fitting with 129 observations."
##              coefficient    std ci_lower ci_upper  p_val sig_level
## (Intercept)      -1.5906 3.7271  -8.8957   5.7146 0.6696    > 0.05
## Age              -0.0053 0.0399  -0.0835   0.0730 0.8954    > 0.05
## countyXuanwe     -0.0470 0.6577  -1.3361   1.2421 0.9431    > 0.05
## BMI               0.0846 0.0778  -0.0678   0.2371 0.2766    > 0.05
## ses              -0.2236 1.0918  -2.3634   1.9163 0.8377    > 0.05
## edu               0.1747 0.4783  -0.7627   1.1122 0.7149    > 0.05
## For AgeAccelGrim :[1] "Fitting with 129 observations."
##              coefficient    std ci_lower ci_upper  p_val sig_level
## (Intercept)      -1.0505 2.4045  -5.7633   3.6623 0.6622    > 0.05
## Age               0.0539 0.0234   0.0080   0.0998 0.0214   <= 0.05
## countyXuanwe     -1.0738 0.5590  -2.1694   0.0218 0.0547    > 0.05
## BMI              -0.1189 0.0652  -0.2468   0.0089 0.0683    > 0.05
## ses               1.7585 0.7244   0.3387   3.1784 0.0152   <= 0.05
## edu              -0.0325 0.2801  -0.5815   0.5164 0.9076    > 0.05
## For DNAmTLAdjAge :[1] "Fitting with 129 observations."
##              coefficient    std ci_lower ci_upper  p_val sig_level
## (Intercept)       0.2668 0.1305   0.0111   0.5226 0.0408   <= 0.05
## Age              -0.0030 0.0014  -0.0057  -0.0003 0.0274   <= 0.05
## countyXuanwe      0.0277 0.0351  -0.0411   0.0965 0.4301    > 0.05
## BMI              -0.0016 0.0041  -0.0095   0.0063 0.6937    > 0.05
## ses              -0.0198 0.0493  -0.1165   0.0769 0.6879    > 0.05
## edu              -0.0246 0.0152  -0.0545   0.0052 0.1056    > 0.05
## For IEAA :[1] "Fitting with 129 observations."
##              coefficient    std ci_lower ci_upper  p_val sig_level
## (Intercept)       0.3629 4.8675  -9.1774   9.9031 0.9406    > 0.05
## Age               0.0186 0.0420  -0.0636   0.1009 0.6571    > 0.05
## countyXuanwe     -0.6249 0.7946  -2.1824   0.9325 0.4316    > 0.05
## BMI              -0.0702 0.1301  -0.3251   0.1848 0.5897    > 0.05
## ses               1.8296 1.2467  -0.6140   4.2732 0.1422    > 0.05
## edu              -0.2049 0.5077  -1.2000   0.7902 0.6866    > 0.05
## For EEAA :[1] "Fitting with 129 observations."
##              coefficient    std ci_lower ci_upper  p_val sig_level
## (Intercept)      -6.8361 5.1177 -16.8669   3.1947 0.1816    > 0.05
## Age               0.0710 0.0476  -0.0223   0.1643 0.1358    > 0.05
## countyXuanwe      0.6297 1.0042  -1.3387   2.5980 0.5307    > 0.05
## BMI               0.0083 0.1160  -0.2190   0.2357 0.9428    > 0.05
## ses               0.2458 1.4845  -2.6640   3.1555 0.8685    > 0.05
## edu               1.2008 0.6229  -0.0202   2.4218 0.0539    > 0.05

1.3. 5MC ~ confounders

## For cur_5mc :[1] "Fitting with 129 observations."
##              coefficient    std ci_lower ci_upper  p_val sig_level
## (Intercept)      18.2037 4.7051   8.9817  27.4257 0.0001  <= 0.001
## Age              -0.0869 0.0348  -0.1551  -0.0187 0.0125   <= 0.05
## countyXuanwe      0.7541 0.7996  -0.8132   2.3213 0.3457    > 0.05
## BMI              -0.2026 0.1302  -0.4578   0.0526 0.1196    > 0.05
## ses              -1.6191 1.1106  -3.7958   0.5576 0.1449    > 0.05
## edu              -0.2050 0.4356  -1.0588   0.6488 0.6379    > 0.05
## For cum_5mc :[1] "Fitting with 129 observations."
##              coefficient      std ci_lower ci_upper  p_val sig_level
## (Intercept)     205.6981 132.0974 -53.2128 464.6090 0.1194    > 0.05
## Age               3.1286   1.0698   1.0318   5.2254 0.0034   <= 0.01
## countyXuanwe     22.2370  26.7781 -30.2481  74.7222 0.4063    > 0.05
## BMI              -3.7026   3.9015 -11.3496   3.9444 0.3426    > 0.05
## ses             -30.6554  34.5139 -98.3026  36.9919 0.3744    > 0.05
## edu             -20.3137  13.3902 -46.5585   5.9311 0.1293    > 0.05
## For bir_5mc :[1] "Fitting with 129 observations."
##              coefficient    std ci_lower ci_upper  p_val sig_level
## (Intercept)       6.3683 1.9366   2.5726  10.1641 0.0010   <= 0.01
## Age              -0.0053 0.0217  -0.0478   0.0372 0.8072    > 0.05
## countyXuanwe      0.3936 0.5482  -0.6809   1.4681 0.4728    > 0.05
## BMI              -0.0093 0.0294  -0.0669   0.0483 0.7513    > 0.05
## ses              -0.0277 0.7455  -1.4889   1.4334 0.9703    > 0.05
## edu              -0.6050 0.2810  -1.1558  -0.0542 0.0313   <= 0.05
## For cur_5mc_measured :[1] "Fitting with 129 observations."
##              coefficient     std ci_lower ci_upper  p_val sig_level
## (Intercept)      22.7197 33.0223 -42.0041  87.4434 0.4914    > 0.05
## Age               0.1417  0.2671  -0.3818   0.6651 0.5958    > 0.05
## countyXuanwe     19.2364 15.8034 -11.7384  50.2111 0.2235    > 0.05
## BMI              -1.2999  1.3304  -3.9075   1.3078 0.3286    > 0.05
## ses             -10.3530 12.6056 -35.0601  14.3540 0.4115    > 0.05
## edu               4.7439  5.9214  -6.8620  16.3499 0.4230    > 0.05

1.4. clusCUR6 ~ confounders

## For CUR6_BC_PAH6 :[1] "Fitting with 129 observations."
##              coefficient    std ci_lower ci_upper  p_val sig_level
## (Intercept)       0.1220 0.8080  -1.4617   1.7056 0.8800    > 0.05
## Age               0.0056 0.0073  -0.0087   0.0200 0.4413    > 0.05
## countyXuanwe      0.6166 0.1783   0.2670   0.9662 0.0005  <= 0.001
## BMI              -0.0183 0.0242  -0.0658   0.0292 0.4496    > 0.05
## ses               0.1067 0.2137  -0.3122   0.5256 0.6176    > 0.05
## edu              -0.1204 0.1175  -0.3507   0.1098 0.3053    > 0.05
## For CUR6_PAH31 :[1] "Fitting with 129 observations."
##              coefficient    std ci_lower ci_upper  p_val sig_level
## (Intercept)       2.0273 0.9878   0.0912   3.9635 0.0401   <= 0.05
## Age              -0.0135 0.0080  -0.0291   0.0022 0.0920    > 0.05
## countyXuanwe      0.2204 0.1783  -0.1291   0.5699 0.2165    > 0.05
## BMI              -0.0445 0.0280  -0.0994   0.0104 0.1121    > 0.05
## ses              -0.2465 0.2252  -0.6880   0.1950 0.2738    > 0.05
## edu              -0.0588 0.1113  -0.2769   0.1593 0.5973    > 0.05
## For CUR6_NkF :[1] "Fitting with 129 observations."
##              coefficient    std ci_lower ci_upper  p_val sig_level
## (Intercept)       1.9227 1.0706  -0.1757   4.0211 0.0725    > 0.05
## Age              -0.0159 0.0091  -0.0338   0.0020 0.0817    > 0.05
## countyXuanwe     -0.1341 0.2108  -0.5473   0.2792 0.5249    > 0.05
## BMI              -0.0460 0.0337  -0.1120   0.0200 0.1720    > 0.05
## ses              -0.1538 0.2925  -0.7272   0.4195 0.5990    > 0.05
## edu               0.0429 0.1330  -0.2178   0.3036 0.7469    > 0.05
## For CUR6_PM_RET :[1] "Fitting with 129 observations."
##              coefficient    std ci_lower ci_upper  p_val sig_level
## (Intercept)       1.0848 0.8239  -0.5300   2.6996 0.1879    > 0.05
## Age              -0.0026 0.0105  -0.0233   0.0180 0.8016    > 0.05
## countyXuanwe     -0.3492 0.1920  -0.7255   0.0271 0.0689    > 0.05
## BMI              -0.0296 0.0203  -0.0695   0.0102 0.1450    > 0.05
## ses              -0.0696 0.2933  -0.6444   0.5053 0.8125    > 0.05
## edu              -0.0561 0.0955  -0.2434   0.1311 0.5567    > 0.05
## For CUR6_NO2 :[1] "Fitting with 129 observations."
##              coefficient    std ci_lower ci_upper  p_val sig_level
## (Intercept)       0.5912 0.8152  -1.0066   2.1890 0.4683    > 0.05
## Age               0.0010 0.0077  -0.0142   0.0161 0.8997    > 0.05
## countyXuanwe     -0.7820 0.1846  -1.1438  -0.4202 0.0000  <= 0.001
## BMI               0.0004 0.0231  -0.0449   0.0457 0.9866    > 0.05
## ses              -0.2588 0.2266  -0.7030   0.1855 0.2536    > 0.05
## edu              -0.0302 0.1412  -0.3069   0.2466 0.8307    > 0.05
## For CUR6_SO2 :[1] "Fitting with 129 observations."
##              coefficient    std ci_lower ci_upper  p_val sig_level
## (Intercept)       0.4673 0.7815  -1.0644   1.9990 0.5499    > 0.05
## Age              -0.0071 0.0091  -0.0249   0.0106 0.4308    > 0.05
## countyXuanwe     -0.4356 0.1658  -0.7605  -0.1108 0.0086   <= 0.01
## BMI               0.0033 0.0097  -0.0157   0.0222 0.7365    > 0.05
## ses              -0.3479 0.2257  -0.7903   0.0945 0.1232    > 0.05
## edu               0.0512 0.1278  -0.1994   0.3017 0.6890    > 0.05

2.1. Current (self-reported) fuel type

The numbers of observations with each current fuel type:

## 
## Other Smoky 
##    25    87

Primary analysis

Investigate the association with current (self-reported) fuel type in the LEX study participants, adjusting for known confounders. The reference group for this analysis would be the smoky coal users. This would be a categorical analysis, and the results would be a p-value from the likelihood ratio (LR) test of a confounder-only model to a model including the exposure variables, as well as p-values for the contrast of each category of coal use (smokeless coal or plant/wood) to that of smoky coal. FDR correction should be used separately for each of these sets. The main interest would be in the coal-specific findings and perhaps less so in the results from the LR test.

GEE (with confounders)

In this section, we perform the generalized estimating equations (GEE) to evaluate the associations between current fuel type and each Epigenetic Age Acceleration with the formula: \[ \begin{aligned} Y = & \beta_0 + \beta_1 * I(\text{Smoky}) \\ & + \beta_2 * county + \beta_3 * BMI + \beta_4 * ses + \beta_5 * edu + \epsilon \end{aligned} \]

Results:

## [1] "Fitting with 112 observations."
## [1] "Fitting with 112 observations."
## [1] "Fitting with 112 observations."
## [1] "Fitting with 112 observations."
## [1] "Fitting with 112 observations."
## [1] "Fitting with 112 observations."
## [1] "Fitting with 112 observations."
## [1] "Fitting with 112 observations."
## Average EAA difference of current Smoky fuel type compared to Other fuel types

## The estimated average EAA differences of Smoky fuel type to other fuel yupes:
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -1.7430 1.2121  -4.1186   0.6327 0.1504
## AgeAccelerationResidualHannum     -0.7802 0.9781  -2.6973   1.1368 0.4250
## AgeAccelPheno                      1.1300 0.8623  -0.5601   2.8200 0.1900
## DNAmAgeSkinBloodClockAdjAge       -0.0362 1.0188  -2.0330   1.9606 0.9717
## AgeAccelGrim                       0.7832 0.7426  -0.6723   2.2387 0.2916
## DNAmTLAdjAge                      -0.0412 0.0561  -0.1512   0.0689 0.4634
## IEAA                              -1.0782 1.1069  -3.2477   1.0913 0.3300
## EEAA                              -1.0279 1.2766  -3.5301   1.4743 0.4207
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05

Sensitivity analyses

GEE (no confounders)

In this section, we perform the generalized estimating equations (GEE) to evaluate the associations between current fuel type and each Epigenetic Age Acceleration with the formula: \[ \begin{aligned} Y = & \beta_0 + \beta_1 * I(\text{Smoky}) \\ & + \epsilon \end{aligned} \]

Results:

## [1] "Fitting with 112 observations."
## [1] "Fitting with 112 observations."
## [1] "Fitting with 112 observations."
## [1] "Fitting with 112 observations."
## [1] "Fitting with 112 observations."
## [1] "Fitting with 112 observations."
## [1] "Fitting with 112 observations."
## [1] "Fitting with 112 observations."
## Average EAA difference of current Smoky fuel type compared to Other fuel types

## The estimated average EAA differences of Smoky fuel type to other fuel yupes:
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -1.1715 1.2244  -3.5713   1.2283 0.3387
## AgeAccelerationResidualHannum     -0.7633 0.9738  -2.6720   1.1454 0.4332
## AgeAccelPheno                      0.3783 0.8418  -1.2716   2.0283 0.6531
## DNAmAgeSkinBloodClockAdjAge       -0.0315 0.9999  -1.9914   1.9284 0.9749
## AgeAccelGrim                       0.5425 0.6538  -0.7389   1.8239 0.4066
## DNAmTLAdjAge                      -0.0134 0.0507  -0.1128   0.0861 0.7924
## IEAA                              -1.0305 1.0822  -3.1517   1.0907 0.3410
## EEAA                              -0.7884 1.2234  -3.1862   1.6094 0.5193
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05

2.2. Childhood (self-reported) fuel type

The numbers of observations with each current fuel type:

## 
## Other Smoky 
##    69    47

Primary analysis

GEE (with confounders)

In this section, we perform the generalized estimating equations (GEE) to evaluate the associations between current fuel type and each Epigenetic Age Acceleration with the formula: \[ \begin{aligned} Y = & \beta_0 + \beta_1 * I(\text{Smoky}) \\ & + \beta_2 * county + \beta_3 * BMI + \beta_4 * ses + \beta_5 * edu + \epsilon \end{aligned} \]

Results:

## [1] "Fitting with 116 observations."
## [1] "Fitting with 116 observations."
## [1] "Fitting with 116 observations."
## [1] "Fitting with 116 observations."
## [1] "Fitting with 116 observations."
## [1] "Fitting with 116 observations."
## [1] "Fitting with 116 observations."
## [1] "Fitting with 116 observations."
## Average EAA difference of birth Smoky fuel type compared to Other fuel types

## The estimated average EAA differences of Smoky fuel type to other fuel yupes:
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.6600 0.8933  -2.4108   1.0908 0.4600
## AgeAccelerationResidualHannum      0.4923 0.8439  -1.1616   2.1463 0.5596
## AgeAccelPheno                      0.6256 0.8687  -1.0770   2.3282 0.4714
## DNAmAgeSkinBloodClockAdjAge        0.8252 0.7592  -0.6628   2.3132 0.2771
## AgeAccelGrim                       1.3711 0.5165   0.3588   2.3834 0.0079
## DNAmTLAdjAge                      -0.0368 0.0340  -0.1034   0.0298 0.2784
## IEAA                              -1.0829 0.8341  -2.7177   0.5520 0.1942
## EEAA                               0.6199 1.0698  -1.4769   2.7166 0.5623
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                    <= 0.01
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05

Sensitivity analyses

GEE (no confounders)

In this section, we perform the generalized estimating equations (GEE) to evaluate the associations between current fuel type and each Epigenetic Age Acceleration with the formula: \[ \begin{aligned} Y = & \beta_0 + \beta_1 * I(\text{Smoky}) \\ & + \epsilon \end{aligned} \]

Results:

## [1] "Fitting with 116 observations."
## [1] "Fitting with 116 observations."
## [1] "Fitting with 116 observations."
## [1] "Fitting with 116 observations."
## [1] "Fitting with 116 observations."
## [1] "Fitting with 116 observations."
## [1] "Fitting with 116 observations."
## [1] "Fitting with 116 observations."
## Average EAA difference of birth Smoky fuel type compared to Other fuel types

## The estimated average EAA differences of Smoky fuel type to other fuel yupes:
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.6600 0.8933  -2.4108   1.0908 0.4600
## AgeAccelerationResidualHannum      0.4923 0.8439  -1.1616   2.1463 0.5596
## AgeAccelPheno                      0.6256 0.8687  -1.0770   2.3282 0.4714
## DNAmAgeSkinBloodClockAdjAge        0.8252 0.7592  -0.6628   2.3132 0.2771
## AgeAccelGrim                       1.3711 0.5165   0.3588   2.3834 0.0079
## DNAmTLAdjAge                      -0.0368 0.0340  -0.1034   0.0298 0.2784
## IEAA                              -1.0829 0.8341  -2.7177   0.5520 0.1942
## EEAA                               0.6199 1.0698  -1.4769   2.7166 0.5623
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                    <= 0.01
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05

2.2. Cumulative lifetime (self-reported) fuel type

The numbers of observations with each cumulative lifetime fuel type:

## 
## Other Smoky 
##    82    37

Primary analysis

GEE (with confounders)

In this section, we perform the generalized estimating equations (GEE) to evaluate the associations between current fuel type and each Epigenetic Age Acceleration with the formula: \[ \begin{aligned} Y = & \beta_0 + \beta_1 * I(\text{Smoky}) \\ & + \beta_2 * county + \beta_3 * BMI + \beta_4 * ses + \beta_5 * edu + \epsilon \end{aligned} \]

Results:

## [1] "Fitting with 119 observations."
## [1] "Fitting with 119 observations."
## [1] "Fitting with 119 observations."
## [1] "Fitting with 119 observations."
## [1] "Fitting with 119 observations."
## [1] "Fitting with 119 observations."
## [1] "Fitting with 119 observations."
## [1] "Fitting with 119 observations."
## Average EAA difference of cumulative Smoky fuel type compared to Other fuel types

## The estimated average EAA differences of Smoky fuel type to other fuel yupes:
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.9880 0.9097  -2.7709   0.7949 0.2774
## AgeAccelerationResidualHannum      0.9141 0.8843  -0.8191   2.6473 0.3013
## AgeAccelPheno                      0.6518 0.9611  -1.2321   2.5356 0.4977
## DNAmAgeSkinBloodClockAdjAge        0.2574 0.7736  -1.2589   1.7737 0.7393
## AgeAccelGrim                       1.0455 0.5286   0.0095   2.0816 0.0479
## DNAmTLAdjAge                      -0.0368 0.0324  -0.1004   0.0267 0.2561
## IEAA                              -1.5367 0.8584  -3.2192   0.1458 0.0734
## EEAA                               1.0795 1.1276  -1.1306   3.2896 0.3384
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                    <= 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05

Sensitivity analyses

GEE (no confounders)

In this section, we perform the generalized estimating equations (GEE) to evaluate the associations between current fuel type and each Epigenetic Age Acceleration with the formula: \[ \begin{aligned} Y = & \beta_0 + \beta_1 * I(\text{Smoky}) \\ & + \epsilon \end{aligned} \]

Results:

## [1] "Fitting with 119 observations."
## [1] "Fitting with 119 observations."
## [1] "Fitting with 119 observations."
## [1] "Fitting with 119 observations."
## [1] "Fitting with 119 observations."
## [1] "Fitting with 119 observations."
## [1] "Fitting with 119 observations."
## [1] "Fitting with 119 observations."
## Average EAA difference of cumulative Smoky fuel type compared to Other fuel types

## The estimated average EAA differences of Smoky fuel type to other fuel yupes:
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.4939 0.9175  -2.2922   1.3045 0.5904
## AgeAccelerationResidualHannum      0.8593 0.8547  -0.8159   2.5344 0.3147
## AgeAccelPheno                      0.2212 0.8660  -1.4761   1.9185 0.7984
## DNAmAgeSkinBloodClockAdjAge        0.2575 0.6879  -1.0908   1.6057 0.7082
## AgeAccelGrim                       0.7626 0.5444  -0.3045   1.8296 0.1613
## DNAmTLAdjAge                      -0.0207 0.0342  -0.0877   0.0463 0.5439
## IEAA                              -1.3281 0.8430  -2.9804   0.3242 0.1152
## EEAA                               1.2134 1.0869  -0.9170   3.3438 0.2643
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05

2.4 All plots together

3.1. Clusters based on model-based exposure estimates at or shortly before the visit (clusCUR6)

The file “LEX_clusCUR6.csv” has information on current pollutant exposures, obtained for the 2 years preceding the visit. To reduce multi-collinearity between exposures, exposure prototypes were derived based on hierarchical cluster analysis in combination followed by principal components analysis. These estimates are available for 6 different prototypes (cluster variables) for a total of 161 subjects and 211 visits. The prototypes are labelled as:

CUR6_BC_PAH6 – Black carbon (BC) and 6 PAHs
CUR6_PAH31 – a large cluster of 31 PAHs
CUR6_NkF – NkF only
CUR6_PM_RET – Particulate matter (PM) and retene
CUR6_NO2 – NO2 only
CUR6_SO2 – SO2 only

Summary the exposure estimates:

Other
(N=25)
Smoky
(N=87)
Overall
(N=129)
CUR6_BC_PAH6
Mean (SD) -0.635 (0.887) 0.402 (0.909) 0.191 (0.984)
Median (IQR) -0.900 (1.57) 0.796 (1.28) 0.787 (1.34)
Missing 2 (8.0%) 1 (1.1%) 3 (2.3%)
CUR6_PAH31
Mean (SD) -0.403 (0.977) 0.329 (0.869) 0.179 (0.930)
Median (IQR) -0.614 (1.84) 0.457 (0.653) 0.407 (1.01)
Missing 2 (8.0%) 1 (1.1%) 3 (2.3%)
CUR6_NkF
Mean (SD) -0.135 (1.22) -0.105 (1.09) -0.0907 (1.11)
Median (IQR) 0.109 (0.809) -0.511 (1.46) -0.335 (1.34)
Missing 2 (8.0%) 1 (1.1%) 3 (2.3%)
CUR6_PM_RET
Mean (SD) 0.465 (1.33) -0.192 (0.699) -0.0365 (0.976)
Median (IQR) 0.276 (1.94) -0.325 (0.674) -0.308 (0.907)
Missing 2 (8.0%) 1 (1.1%) 3 (2.3%)
CUR6_NO2
Mean (SD) 0.820 (0.792) 0.0556 (0.993) 0.124 (1.01)
Median (IQR) 0.971 (1.18) -0.0613 (1.01) 0.0190 (1.22)
Missing 2 (8.0%) 1 (1.1%) 3 (2.3%)
CUR6_SO2
Mean (SD) 0.269 (1.18) -0.216 (0.798) -0.135 (0.887)
Median (IQR) 0.177 (2.22) -0.304 (0.980) -0.298 (1.03)
Missing 2 (8.0%) 1 (1.1%) 3 (2.3%)

Primary analysis

GEE (with confounders)

In this section, we perform the generalized estimating equations (GEE) to evaluate the associations between each cluster within current pollutant exposures and each Epigenetic Age Acceleration with the formula: \[ \begin{aligned} Y = & \beta_0 + \beta_1 * X \\ & + \beta_2 * county + \beta_3 * BMI + \beta_4 * ses + \beta_5 * edu + \epsilon \end{aligned} \] where \(Y\) is one of the epigenetic age accelerations and X is one of the cluster estimates.

Results:

## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."

## The estimated effects:
## $CUR6_BC_PAH6
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.4376 0.5530  -1.5214   0.6463 0.4288
## AgeAccelerationResidualHannum     -0.3263 0.4319  -1.1727   0.5201 0.4499
## AgeAccelPheno                      0.1699 0.4560  -0.7239   1.0637 0.7094
## DNAmAgeSkinBloodClockAdjAge       -0.1054 0.3570  -0.8051   0.5942 0.7677
## AgeAccelGrim                       0.7280 0.2647   0.2091   1.2468 0.0060
## DNAmTLAdjAge                       0.0197 0.0208  -0.0210   0.0604 0.3438
## IEAA                              -0.1731 0.4729  -1.0999   0.7538 0.7144
## EEAA                              -0.6292 0.5447  -1.6968   0.4383 0.2480
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                    <= 0.01
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CUR6_PAH31
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.3157 0.5216  -0.7067   1.3382 0.5450
## AgeAccelerationResidualHannum     -0.1466 0.4576  -1.0436   0.7504 0.7487
## AgeAccelPheno                      0.4073 0.4871  -0.5475   1.3620 0.4031
## DNAmAgeSkinBloodClockAdjAge        0.3129 0.3496  -0.3722   0.9981 0.3707
## AgeAccelGrim                       0.8305 0.2287   0.3821   1.2788 0.0003
## DNAmTLAdjAge                      -0.0104 0.0157  -0.0411   0.0204 0.5090
## IEAA                               0.2367 0.5351  -0.8121   1.2855 0.6582
## EEAA                              -0.2610 0.5683  -1.3748   0.8528 0.6461
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                   <= 0.001
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CUR6_NkF
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.1266 0.4508  -1.0101   0.7570 0.7789
## AgeAccelerationResidualHannum     -0.1760 0.4085  -0.9766   0.6246 0.6665
## AgeAccelPheno                     -0.4256 0.3837  -1.1778   0.3265 0.2673
## DNAmAgeSkinBloodClockAdjAge       -0.0851 0.3348  -0.7414   0.5711 0.7993
## AgeAccelGrim                       0.2463 0.2348  -0.2139   0.7066 0.2942
## DNAmTLAdjAge                      -0.0286 0.0167  -0.0613   0.0041 0.0870
## IEAA                              -0.1414 0.3501  -0.8276   0.5447 0.6862
## EEAA                              -0.1996 0.5345  -1.2472   0.8480 0.7088
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CUR6_PM_RET
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.2394 0.4203  -0.5843   1.0632 0.5689
## AgeAccelerationResidualHannum     -0.4501 0.3633  -1.1622   0.2620 0.2154
## AgeAccelPheno                     -0.4008 0.5463  -1.4716   0.6700 0.4632
## DNAmAgeSkinBloodClockAdjAge       -0.3933 0.4285  -1.2331   0.4465 0.3586
## AgeAccelGrim                       0.4174 0.3269  -0.2234   1.0582 0.2017
## DNAmTLAdjAge                       0.0051 0.0206  -0.0353   0.0456 0.8032
## IEAA                               0.3620 0.3769  -0.3767   1.1008 0.3368
## EEAA                              -0.5788 0.5099  -1.5782   0.4206 0.2563
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CUR6_NO2
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.6277 0.4601  -0.2741   1.5295 0.1725
## AgeAccelerationResidualHannum     -0.1788 0.3989  -0.9607   0.6030 0.6539
## AgeAccelPheno                      0.0840 0.5150  -0.9255   1.0935 0.8704
## DNAmAgeSkinBloodClockAdjAge        0.2779 0.3567  -0.4213   0.9771 0.4360
## AgeAccelGrim                      -0.2031 0.2992  -0.7895   0.3832 0.4971
## DNAmTLAdjAge                       0.0241 0.0186  -0.0123   0.0605 0.1937
## IEAA                               0.4382 0.4023  -0.3503   1.2268 0.2761
## EEAA                              -0.2345 0.5714  -1.3543   0.8854 0.6815
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CUR6_SO2
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.2692 0.4852  -1.2201   0.6818 0.5790
## AgeAccelerationResidualHannum     -0.3495 0.5162  -1.3612   0.6622 0.4983
## AgeAccelPheno                     -0.7417 0.5946  -1.9072   0.4237 0.2122
## DNAmAgeSkinBloodClockAdjAge       -0.4359 0.4445  -1.3070   0.4353 0.3268
## AgeAccelGrim                      -0.6161 0.3067  -1.2173  -0.0149 0.0446
## DNAmTLAdjAge                       0.0017 0.0201  -0.0376   0.0411 0.9307
## IEAA                              -0.4774 0.4466  -1.3527   0.3979 0.2851
## EEAA                              -0.4778 0.6074  -1.6684   0.7128 0.4315
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                    <= 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05

GEE (Mix, mutual adjust)

In this section, we perform the generalized estimating equations (GEE) to evaluate the associations between each cluster within current pollutant exposures and each Epigenetic Age Acceleration with the formula: \[ \begin{aligned} Y = & \beta_0 + \beta_1 * BC\_PAH6 + \beta_2 PAH31 + \beta_3 NkF + \beta_4 PM\_RET + \beta_5 NO2 + \beta_6 SO2 \\ & + \beta_7 * county + \beta_8 * BMI + \beta_9 * ses + \beta_10 * edu + \epsilon \end{aligned} \] where \(Y\) is one of the epigenetic age accelerations.

Results:

## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."

## The estimated effects:
## $CUR6_BC_PAH6
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -1.4737 0.9206  -3.2780   0.3307 0.1094
## AgeAccelerationResidualHannum     -0.9270 0.6848  -2.2692   0.4152 0.1758
## AgeAccelPheno                     -0.9852 0.6082  -2.1773   0.2069 0.1053
## DNAmAgeSkinBloodClockAdjAge       -0.9189 0.6919  -2.2751   0.4372 0.1841
## AgeAccelGrim                       0.4061 0.4412  -0.4587   1.2709 0.3574
## DNAmTLAdjAge                       0.0279 0.0305  -0.0318   0.0876 0.3592
## IEAA                              -0.9452 0.6561  -2.2312   0.3407 0.1497
## EEAA                              -1.5190 0.8958  -3.2747   0.2367 0.0899
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CUR6_PAH31
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            1.1989 0.8218  -0.4119   2.8096 0.1446
## AgeAccelerationResidualHannum      0.7096 0.7499  -0.7601   2.1793 0.3440
## AgeAccelPheno                      1.5803 0.7041   0.2002   2.9603 0.0248
## DNAmAgeSkinBloodClockAdjAge        1.3248 0.6372   0.0759   2.5736 0.0376
## AgeAccelGrim                       0.5440 0.4338  -0.3061   1.3942 0.2097
## DNAmTLAdjAge                      -0.0276 0.0273  -0.0811   0.0260 0.3131
## IEAA                               0.6350 0.7860  -0.9056   2.1755 0.4192
## EEAA                               0.9887 0.9497  -0.8727   2.8501 0.2979
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                   <= 0.05
## DNAmAgeSkinBloodClockAdjAge     <= 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CUR6_NkF
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.7286 0.6667  -2.0352   0.5781 0.2745
## AgeAccelerationResidualHannum     -0.2519 0.5948  -1.4178   0.9139 0.6719
## AgeAccelPheno                     -0.6084 0.4813  -1.5517   0.3350 0.2062
## DNAmAgeSkinBloodClockAdjAge       -0.1911 0.5542  -1.2774   0.8952 0.7303
## AgeAccelGrim                       0.2605 0.3510  -0.4275   0.9485 0.4581
## DNAmTLAdjAge                      -0.0258 0.0193  -0.0636   0.0120 0.1805
## IEAA                              -0.5414 0.4452  -1.4139   0.3312 0.2239
## EEAA                              -0.3847 0.7444  -1.8438   1.0743 0.6053
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CUR6_PM_RET
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.0725 0.6160  -1.2800   1.1349 0.9063
## AgeAccelerationResidualHannum     -0.6829 0.5457  -1.7525   0.3866 0.2107
## AgeAccelPheno                     -1.0891 0.6160  -2.2965   0.1184 0.0771
## DNAmAgeSkinBloodClockAdjAge       -1.1383 0.5841  -2.2831   0.0064 0.0513
## AgeAccelGrim                      -0.0872 0.4119  -0.8946   0.7201 0.8323
## DNAmTLAdjAge                       0.0233 0.0255  -0.0267   0.0733 0.3608
## IEAA                               0.2121 0.6030  -0.9697   1.3940 0.7250
## EEAA                              -0.8583 0.7149  -2.2595   0.5430 0.2299
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CUR6_NO2
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.5896 0.4827  -0.3565   1.5356 0.2219
## AgeAccelerationResidualHannum      0.0024 0.4451  -0.8701   0.8749 0.9957
## AgeAccelPheno                      0.3660 0.5295  -0.6717   1.4038 0.4894
## DNAmAgeSkinBloodClockAdjAge        0.5382 0.3939  -0.2339   1.3103 0.1719
## AgeAccelGrim                      -0.1729 0.3181  -0.7964   0.4505 0.5867
## DNAmTLAdjAge                       0.0234 0.0190  -0.0138   0.0607 0.2180
## IEAA                               0.4154 0.4241  -0.4157   1.2466 0.3273
## EEAA                              -0.0089 0.5870  -1.1595   1.1417 0.9879
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CUR6_SO2
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.7385 0.6447  -2.0020   0.5250 0.2520
## AgeAccelerationResidualHannum     -0.7789 0.5943  -1.9437   0.3859 0.1900
## AgeAccelPheno                     -1.1245 0.5424  -2.1876  -0.0614 0.0381
## DNAmAgeSkinBloodClockAdjAge       -0.9798 0.5251  -2.0091   0.0494 0.0621
## AgeAccelGrim                      -0.3753 0.2898  -0.9434   0.1928 0.1954
## DNAmTLAdjAge                       0.0156 0.0216  -0.0266   0.0579 0.4686
## IEAA                              -0.7230 0.5661  -1.8325   0.3865 0.2015
## EEAA                              -1.1491 0.6975  -2.5161   0.2180 0.0995
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                   <= 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05

Sensitivity analyses

GEE (No confounders)

In this section, we perform the generalized estimating equations (GEE) to evaluate the associations between each cluster within current pollutant exposures and each Epigenetic Age Acceleration with the formula: \[ \begin{aligned} Y = & \beta_0 + \beta_1 * X + \epsilon \end{aligned} \] where \(Y\) is one of the epigenetic age accelerations and X is one of the cluster estimates.

Results:

## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."

## The estimated effects:
## $CUR6_BC_PAH6
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.4396 0.5345  -1.4872   0.6081 0.4109
## AgeAccelerationResidualHannum     -0.2580 0.3996  -1.0413   0.5252 0.5185
## AgeAccelPheno                      0.0509 0.4304  -0.7927   0.8945 0.9058
## DNAmAgeSkinBloodClockAdjAge       -0.1448 0.3542  -0.8391   0.5494 0.6826
## AgeAccelGrim                       0.5122 0.2570   0.0084   1.0160 0.0463
## DNAmTLAdjAge                       0.0227 0.0185  -0.0135   0.0590 0.2186
## IEAA                              -0.2102 0.4619  -1.1156   0.6952 0.6491
## EEAA                              -0.5111 0.4941  -1.4795   0.4573 0.3009
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                    <= 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CUR6_PAH31
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.3145 0.5218  -0.7083   1.3373 0.5467
## AgeAccelerationResidualHannum     -0.1046 0.4359  -0.9589   0.7497 0.8104
## AgeAccelPheno                      0.3448 0.4782  -0.5924   1.2820 0.4708
## DNAmAgeSkinBloodClockAdjAge        0.2551 0.3535  -0.4378   0.9479 0.4706
## AgeAccelGrim                       0.7856 0.2480   0.2996   1.2717 0.0015
## DNAmTLAdjAge                      -0.0081 0.0165  -0.0403   0.0242 0.6246
## IEAA                               0.2237 0.5316  -0.8182   1.2657 0.6739
## EEAA                              -0.1931 0.5304  -1.2327   0.8466 0.7159
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                    <= 0.01
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CUR6_NkF
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.0060 0.4487  -0.8855   0.8736 0.9894
## AgeAccelerationResidualHannum     -0.1703 0.3897  -0.9341   0.5935 0.6620
## AgeAccelPheno                     -0.4435 0.3869  -1.2018   0.3147 0.2516
## DNAmAgeSkinBloodClockAdjAge       -0.0936 0.3238  -0.7281   0.5410 0.7726
## AgeAccelGrim                       0.2990 0.2516  -0.1942   0.7922 0.2347
## DNAmTLAdjAge                      -0.0283 0.0162  -0.0601   0.0035 0.0811
## IEAA                              -0.0708 0.3596  -0.7757   0.6341 0.8439
## EEAA                              -0.1679 0.5151  -1.1775   0.8417 0.7444
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CUR6_PM_RET
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.2446 0.4092  -0.5575   1.0467 0.5501
## AgeAccelerationResidualHannum     -0.4462 0.3719  -1.1751   0.2827 0.2302
## AgeAccelPheno                     -0.3131 0.5385  -1.3685   0.7424 0.5610
## DNAmAgeSkinBloodClockAdjAge       -0.4074 0.4180  -1.2266   0.4118 0.3297
## AgeAccelGrim                       0.5359 0.3358  -0.1222   1.1940 0.1105
## DNAmTLAdjAge                       0.0016 0.0198  -0.0371   0.0404 0.9343
## IEAA                               0.4289 0.3790  -0.3140   1.1718 0.2578
## EEAA                              -0.6026 0.5104  -1.6030   0.3977 0.2377
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CUR6_NO2
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.4110 0.3834  -0.3405   1.1625 0.2837
## AgeAccelerationResidualHannum     -0.1603 0.3554  -0.8570   0.5364 0.6520
## AgeAccelPheno                      0.2724 0.4317  -0.5738   1.1185 0.5281
## DNAmAgeSkinBloodClockAdjAge        0.2290 0.2794  -0.3185   0.7766 0.4124
## AgeAccelGrim                       0.0075 0.3039  -0.5882   0.6031 0.9804
## DNAmTLAdjAge                       0.0108 0.0163  -0.0211   0.0426 0.5079
## IEAA                               0.3776 0.3666  -0.3410   1.0962 0.3031
## EEAA                              -0.2774 0.4852  -1.2285   0.6736 0.5675
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CUR6_SO2
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.3262 0.4740  -1.2553   0.6029 0.4913
## AgeAccelerationResidualHannum     -0.2930 0.4921  -1.2574   0.6714 0.5515
## AgeAccelPheno                     -0.5203 0.5847  -1.6663   0.6257 0.3735
## DNAmAgeSkinBloodClockAdjAge       -0.3625 0.4188  -1.1834   0.4585 0.3868
## AgeAccelGrim                      -0.4774 0.2869  -1.0398   0.0850 0.0962
## DNAmTLAdjAge                      -0.0057 0.0182  -0.0414   0.0300 0.7556
## IEAA                              -0.4681 0.4600  -1.3697   0.4336 0.3089
## EEAA                              -0.4333 0.5659  -1.5425   0.6759 0.4439
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05

GEE (No confounders, mutual adjust)

In this section, we perform the generalized estimating equations (GEE) to evaluate the associations between each cluster within current pollutant exposures and each Epigenetic Age Acceleration with the formula: \[ \begin{aligned} Y = & \beta_0 + \beta_1 * BC\_PAH6 + \beta_2 PAH31 + \beta_3 NkF + \beta_4 PM\_RET + \beta_5 NO2 + \beta_6 SO2 \\ & + \epsilon \end{aligned} \] where \(Y\) is one of the epigenetic age accelerations.

Results:

## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."

## The estimated effects:
## $CUR6_BC_PAH6
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -1.5027 0.9467  -3.3582   0.3528 0.1124
## AgeAccelerationResidualHannum     -0.9039 0.6494  -2.1767   0.3690 0.1640
## AgeAccelPheno                     -1.0664 0.6256  -2.2926   0.1598 0.0883
## DNAmAgeSkinBloodClockAdjAge       -0.9810 0.6840  -2.3217   0.3597 0.1515
## AgeAccelGrim                       0.2155 0.4685  -0.7027   1.1337 0.6455
## DNAmTLAdjAge                       0.0325 0.0287  -0.0238   0.0888 0.2579
## IEAA                              -0.9745 0.6933  -2.3335   0.3844 0.1599
## EEAA                              -1.4906 0.8365  -3.1302   0.1489 0.0748
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CUR6_PAH31
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            1.2535 0.8323  -0.3779   2.8848 0.1321
## AgeAccelerationResidualHannum      0.7478 0.7111  -0.6459   2.1415 0.2930
## AgeAccelPheno                      1.5098 0.7000   0.1378   2.8818 0.0310
## DNAmAgeSkinBloodClockAdjAge        1.3110 0.6359   0.0646   2.5573 0.0392
## AgeAccelGrim                       0.4510 0.4652  -0.4608   1.3629 0.3323
## DNAmTLAdjAge                      -0.0249 0.0273  -0.0784   0.0285 0.3602
## IEAA                               0.6306 0.7935  -0.9247   2.1858 0.4268
## EEAA                               1.0742 0.8978  -0.6854   2.8338 0.2315
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                   <= 0.05
## DNAmAgeSkinBloodClockAdjAge     <= 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CUR6_NkF
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.5894 0.6960  -1.9535   0.7748 0.3971
## AgeAccelerationResidualHannum     -0.2702 0.5732  -1.3936   0.8532 0.6374
## AgeAccelPheno                     -0.7113 0.4819  -1.6557   0.2331 0.1399
## DNAmAgeSkinBloodClockAdjAge       -0.2213 0.5518  -1.3028   0.8602 0.6883
## AgeAccelGrim                       0.1906 0.3893  -0.5725   0.9537 0.6244
## DNAmTLAdjAge                      -0.0211 0.0194  -0.0591   0.0170 0.2771
## IEAA                              -0.4916 0.4720  -1.4167   0.4335 0.2976
## EEAA                              -0.3652 0.7128  -1.7623   1.0318 0.6084
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CUR6_PM_RET
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.1690 0.6407  -1.4248   1.0867 0.7919
## AgeAccelerationResidualHannum     -0.6820 0.5574  -1.7745   0.4105 0.2211
## AgeAccelPheno                     -0.9336 0.5926  -2.0951   0.2279 0.1151
## DNAmAgeSkinBloodClockAdjAge       -1.1297 0.5799  -2.2663   0.0068 0.0514
## AgeAccelGrim                       0.1523 0.4124  -0.6560   0.9605 0.7119
## DNAmTLAdjAge                       0.0160 0.0249  -0.0327   0.0647 0.5201
## IEAA                               0.2398 0.6095  -0.9548   1.4344 0.6940
## EEAA                              -0.9133 0.7266  -2.3375   0.5108 0.2087
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CUR6_NO2
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.4004 0.4516  -0.4848   1.2856 0.3753
## AgeAccelerationResidualHannum      0.0328 0.4317  -0.8133   0.8789 0.9394
## AgeAccelPheno                      0.5882 0.4851  -0.3627   1.5390 0.2253
## DNAmAgeSkinBloodClockAdjAge        0.5715 0.3662  -0.1463   1.2892 0.1186
## AgeAccelGrim                       0.0380 0.3248  -0.5986   0.6745 0.9069
## DNAmTLAdjAge                       0.0132 0.0180  -0.0222   0.0485 0.4660
## IEAA                               0.3475 0.4173  -0.4704   1.1654 0.4050
## EEAA                              -0.0381 0.5511  -1.1183   1.0421 0.9449
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CUR6_SO2
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.9251 0.6431  -2.1855   0.3354 0.1503
## AgeAccelerationResidualHannum     -0.7003 0.5825  -1.8421   0.4414 0.2292
## AgeAccelPheno                     -0.9749 0.5515  -2.0558   0.1061 0.0771
## DNAmAgeSkinBloodClockAdjAge       -0.9567 0.5289  -1.9933   0.0800 0.0705
## AgeAccelGrim                      -0.3026 0.2907  -0.8724   0.2672 0.2979
## DNAmTLAdjAge                       0.0086 0.0224  -0.0353   0.0524 0.7024
## IEAA                              -0.8380 0.5622  -1.9400   0.2639 0.1361
## EEAA                              -1.0844 0.6843  -2.4257   0.2569 0.1131
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05

3.2. Clusters based on model-based exposure estimates accrued before age 18 (clusCHLD5)

The file “LEX_clusCHLD5.csv” has information on estimated pollutant exposures during early childhood. Estimates are available for 5 different prototypes (cluster variables) for a total of 161 subjects and 211 visits. The prototypes are labelled as:

CHLD5_X7 – a cluster of 7 air pollutants
CHLD5_X33 – a large cluster of 33 air pollutants
CHLD5_NkF – NkF only
CHLD5_NO2 – NO2 only
CHLD5_SO2 – SO2 only

Summary the exposure estimates:

Other
(N=25)
Smoky
(N=87)
Overall
(N=129)
CHLD5_X7
Mean (SD) 0.0349 (1.15) -0.107 (0.816) -0.0368 (0.962)
Median (IQR) -0.130 (1.77) 0.0997 (0.798) 0.107 (1.06)
Missing 2 (8.0%) 1 (1.1%) 3 (2.3%)
CHLD5_X33
Mean (SD) -0.211 (0.951) 0.273 (0.993) 0.155 (1.00)
Median (IQR) -0.106 (1.63) 0.507 (1.57) 0.00446 (1.67)
Missing 2 (8.0%) 1 (1.1%) 3 (2.3%)
CHLD5_NkF
Mean (SD) 0.147 (1.44) -0.186 (1.07) -0.109 (1.11)
Median (IQR) 0.0638 (1.20) -0.450 (1.59) -0.244 (1.49)
Missing 2 (8.0%) 1 (1.1%) 3 (2.3%)
CHLD5_NO2
Mean (SD) 0.135 (0.746) 0.294 (1.19) 0.182 (1.09)
Median (IQR) 0.00110 (1.13) 0.434 (1.36) 0.214 (1.27)
Missing 2 (8.0%) 1 (1.1%) 3 (2.3%)
CHLD5_SO2
Mean (SD) 0.382 (1.02) -0.0233 (0.818) 0.00143 (0.914)
Median (IQR) 0.393 (1.07) 0.336 (1.30) 0.331 (1.42)
Missing 2 (8.0%) 1 (1.1%) 3 (2.3%)

Primary analysis

GEE (with confounders)

In this section, we perform the generalized estimating equations (GEE) to evaluate the associations between each cluster within current pollutant exposures and each Epigenetic Age Acceleration with the formula: \[ \begin{aligned} Y = & \beta_0 + \beta_1 * X \\ & + \beta_2 * county + \beta_3 * BMI + \beta_4 * ses + \beta_5 * edu + \epsilon \end{aligned} \] where \(Y\) is one of the epigenetic age accelerations and X is one of the cluster estimates.

Results:

## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."

## The estimated effects:
## $CHLD5_X7
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.3328 0.4935  -0.6345   1.3001 0.5001
## AgeAccelerationResidualHannum      0.2637 0.4528  -0.6238   1.1512 0.5603
## AgeAccelPheno                      0.5901 0.4893  -0.3690   1.5492 0.2278
## DNAmAgeSkinBloodClockAdjAge        0.1253 0.4167  -0.6915   0.9421 0.7636
## AgeAccelGrim                       0.7524 0.2428   0.2766   1.2282 0.0019
## DNAmTLAdjAge                       0.0024 0.0179  -0.0327   0.0375 0.8948
## IEAA                               0.2947 0.4579  -0.6028   1.1922 0.5199
## EEAA                               0.4732 0.5728  -0.6495   1.5959 0.4088
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                    <= 0.01
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CHLD5_X33
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.1751 0.4357  -0.6788   1.0291 0.6877
## AgeAccelerationResidualHannum      0.4233 0.4514  -0.4614   1.3080 0.3484
## AgeAccelPheno                      1.0052 0.4145   0.1928   1.8176 0.0153
## DNAmAgeSkinBloodClockAdjAge        0.6370 0.3423  -0.0339   1.3080 0.0628
## AgeAccelGrim                       0.9202 0.2671   0.3966   1.4438 0.0006
## DNAmTLAdjAge                       0.0017 0.0167  -0.0311   0.0345 0.9178
## IEAA                              -0.1736 0.4286  -1.0136   0.6663 0.6854
## EEAA                               0.6738 0.5461  -0.3965   1.7441 0.2172
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                   <= 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                   <= 0.001
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CHLD5_NkF
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.1088 0.3108  -0.5004   0.7180 0.7263
## AgeAccelerationResidualHannum      0.1589 0.2796  -0.3891   0.7069 0.5698
## AgeAccelPheno                     -0.1006 0.3453  -0.7773   0.5761 0.7708
## DNAmAgeSkinBloodClockAdjAge       -0.1530 0.2998  -0.7407   0.4347 0.6098
## AgeAccelGrim                       0.3441 0.2453  -0.1366   0.8249 0.1606
## DNAmTLAdjAge                      -0.0143 0.0189  -0.0514   0.0228 0.4492
## IEAA                              -0.0039 0.2819  -0.5564   0.5486 0.9890
## EEAA                               0.2225 0.3820  -0.5263   0.9713 0.5603
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CHLD5_NO2
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.0742 0.3383  -0.7374   0.5889 0.8264
## AgeAccelerationResidualHannum      0.1620 0.3611  -0.5457   0.8696 0.6537
## AgeAccelPheno                      0.1014 0.3865  -0.6562   0.8590 0.7931
## DNAmAgeSkinBloodClockAdjAge        0.4688 0.2745  -0.0692   1.0068 0.0876
## AgeAccelGrim                      -0.1935 0.2516  -0.6866   0.2996 0.4419
## DNAmTLAdjAge                       0.0035 0.0168  -0.0295   0.0364 0.8370
## IEAA                              -0.1071 0.2931  -0.6815   0.4673 0.7148
## EEAA                               0.1659 0.4583  -0.7324   1.0642 0.7174
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CHLD5_SO2
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.0506 0.5840  -1.0939   1.1952 0.9309
## AgeAccelerationResidualHannum      0.2753 0.5242  -0.7522   1.3028 0.5995
## AgeAccelPheno                     -0.0021 0.5678  -1.1150   1.1109 0.9971
## DNAmAgeSkinBloodClockAdjAge        0.3932 0.4476  -0.4841   1.2704 0.3797
## AgeAccelGrim                      -0.2606 0.3112  -0.8706   0.3494 0.4024
## DNAmTLAdjAge                       0.0169 0.0215  -0.0252   0.0591 0.4314
## IEAA                              -0.0827 0.5057  -1.0739   0.9086 0.8702
## EEAA                               0.2011 0.6701  -1.1123   1.5144 0.7641
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05

GEE (Mix, mutual adjust)

In this section, we perform the generalized estimating equations (GEE) to evaluate the associations between each cluster within current pollutant exposures and each Epigenetic Age Acceleration with the formula: \[ \begin{aligned} Y = & \beta_0 + \beta_1 * X7 + \beta_2 X33 + \beta_3 NkF + \beta_4 NO2 + \beta_5 SO2 \\ & + \beta_6 * county + \beta_7 * BMI + \beta_8 * ses + \beta_9 * edu + \epsilon \end{aligned} \] where \(Y\) is one of the epigenetic age accelerations.

Results:

## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."

## The estimated effects:
## $CHLD5_X7
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.5375 0.8931  -1.2128   2.2879 0.5472
## AgeAccelerationResidualHannum      0.1518 0.7423  -1.3032   1.6067 0.8380
## AgeAccelPheno                     -0.0683 0.8290  -1.6931   1.5564 0.9343
## DNAmAgeSkinBloodClockAdjAge       -0.2038 0.7377  -1.6496   1.2421 0.7824
## AgeAccelGrim                      -0.0784 0.4170  -0.8957   0.7388 0.8508
## DNAmTLAdjAge                       0.0299 0.0316  -0.0320   0.0919 0.3436
## IEAA                               0.9570 0.7586  -0.5299   2.4439 0.2071
## EEAA                               0.1483 0.9876  -1.7874   2.0840 0.8807
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CHLD5_X33
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.1380 0.7662  -1.6397   1.3637 0.8571
## AgeAccelerationResidualHannum      0.3045 0.5969  -0.8656   1.4745 0.6100
## AgeAccelPheno                      1.0626 0.6752  -0.2607   2.3859 0.1155
## DNAmAgeSkinBloodClockAdjAge        0.7032 0.6049  -0.4824   1.8888 0.2450
## AgeAccelGrim                       1.0012 0.3620   0.2917   1.7107 0.0057
## DNAmTLAdjAge                      -0.0164 0.0267  -0.0687   0.0359 0.5378
## IEAA                              -0.7277 0.6455  -1.9929   0.5374 0.2596
## EEAA                               0.5607 0.7685  -0.9456   2.0670 0.4657
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                    <= 0.01
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CHLD5_NkF
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.0063 0.3320  -0.6570   0.6445 0.9849
## AgeAccelerationResidualHannum      0.1633 0.3060  -0.4365   0.7631 0.5937
## AgeAccelPheno                     -0.1277 0.3559  -0.8253   0.5699 0.7197
## DNAmAgeSkinBloodClockAdjAge       -0.0446 0.2848  -0.6028   0.5136 0.8755
## AgeAccelGrim                       0.2820 0.2503  -0.2085   0.7725 0.2599
## DNAmTLAdjAge                      -0.0192 0.0207  -0.0597   0.0214 0.3543
## IEAA                              -0.2063 0.2997  -0.7937   0.3811 0.4913
## EEAA                               0.2126 0.4238  -0.6181   1.0432 0.6160
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CHLD5_NO2
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.1139 0.3990  -0.8960   0.6682 0.7753
## AgeAccelerationResidualHannum      0.0468 0.3577  -0.6544   0.7479 0.8960
## AgeAccelPheno                     -0.0169 0.4297  -0.8591   0.8253 0.9686
## DNAmAgeSkinBloodClockAdjAge        0.3188 0.2924  -0.2543   0.8919 0.2756
## AgeAccelGrim                      -0.2023 0.2516  -0.6955   0.2909 0.4215
## DNAmTLAdjAge                      -0.0052 0.0197  -0.0438   0.0334 0.7926
## IEAA                              -0.0469 0.3722  -0.7764   0.6825 0.8997
## EEAA                               0.0635 0.4602  -0.8386   0.9655 0.8903
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CHLD5_SO2
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.3605 0.7571  -1.1235   1.8444 0.6340
## AgeAccelerationResidualHannum      0.3247 0.6999  -1.0471   1.6965 0.6427
## AgeAccelPheno                     -0.1531 0.6274  -1.3829   1.0767 0.8072
## DNAmAgeSkinBloodClockAdjAge        0.0504 0.5068  -0.9429   1.0438 0.9207
## AgeAccelGrim                      -0.2171 0.3720  -0.9463   0.5120 0.5595
## DNAmTLAdjAge                       0.0305 0.0295  -0.0274   0.0883 0.3025
## IEAA                               0.3832 0.6912  -0.9715   1.7380 0.5793
## EEAA                               0.2247 0.8796  -1.4994   1.9487 0.7984
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05

Sensitivity analyses

GEE (No confounders)

In this section, we perform the generalized estimating equations (GEE) to evaluate the associations between each cluster within current pollutant exposures and each Epigenetic Age Acceleration with the formula: \[ \begin{aligned} Y = & \beta_0 + \beta_1 * X \\ & + \epsilon \end{aligned} \] where \(Y\) is one of the epigenetic age accelerations and X is one of the cluster estimates.

Results:

## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."

## The estimated effects:
## $CHLD5_X7
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.2293 0.5142  -0.7785   1.2371 0.6556
## AgeAccelerationResidualHannum      0.2397 0.4451  -0.6328   1.1121 0.5903
## AgeAccelPheno                      0.6099 0.4913  -0.3530   1.5728 0.2144
## DNAmAgeSkinBloodClockAdjAge        0.1010 0.4283  -0.7385   0.9406 0.8136
## AgeAccelGrim                       0.7497 0.2581   0.2438   1.2555 0.0037
## DNAmTLAdjAge                       0.0029 0.0177  -0.0318   0.0376 0.8697
## IEAA                               0.2553 0.4845  -0.6943   1.2049 0.5982
## EEAA                               0.3994 0.5642  -0.7064   1.5053 0.4790
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                    <= 0.01
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CHLD5_X33
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.0507 0.4348  -0.8016   0.9029 0.9072
## AgeAccelerationResidualHannum      0.3471 0.4259  -0.4876   1.1818 0.4150
## AgeAccelPheno                      0.9328 0.3808   0.1864   1.6792 0.0143
## DNAmAgeSkinBloodClockAdjAge        0.5351 0.3289  -0.1095   1.1796 0.1037
## AgeAccelGrim                       0.8261 0.2839   0.2697   1.3824 0.0036
## DNAmTLAdjAge                       0.0051 0.0156  -0.0256   0.0357 0.7466
## IEAA                              -0.1730 0.4338  -1.0233   0.6774 0.6901
## EEAA                               0.5122 0.5165  -0.5001   1.5246 0.3213
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                   <= 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                    <= 0.01
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CHLD5_NkF
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.0968 0.3240  -0.5383   0.7319 0.7652
## AgeAccelerationResidualHannum      0.1682 0.2946  -0.4092   0.7455 0.5681
## AgeAccelPheno                     -0.0094 0.3524  -0.7002   0.6813 0.9786
## DNAmAgeSkinBloodClockAdjAge       -0.1291 0.2767  -0.6714   0.4132 0.6407
## AgeAccelGrim                       0.4118 0.2605  -0.0988   0.9223 0.1139
## DNAmTLAdjAge                      -0.0185 0.0168  -0.0515   0.0144 0.2699
## IEAA                              -0.0035 0.2869  -0.5658   0.5589 0.9904
## EEAA                               0.2252 0.3959  -0.5508   1.0013 0.5695
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CHLD5_NO2
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.2672 0.3047  -0.8644   0.3300 0.3806
## AgeAccelerationResidualHannum      0.0791 0.3128  -0.5339   0.6922 0.8002
## AgeAccelPheno                      0.2578 0.3457  -0.4198   0.9354 0.4559
## DNAmAgeSkinBloodClockAdjAge        0.4077 0.2391  -0.0609   0.8763 0.0881
## AgeAccelGrim                      -0.1213 0.2123  -0.5374   0.2948 0.5679
## DNAmTLAdjAge                      -0.0006 0.0154  -0.0308   0.0297 0.9705
## IEAA                              -0.1234 0.2624  -0.6378   0.3909 0.6381
## EEAA                              -0.0305 0.4107  -0.8355   0.7745 0.9408
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CHLD5_SO2
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.2661 0.5452  -1.3346   0.8025 0.6255
## AgeAccelerationResidualHannum      0.2676 0.4355  -0.5859   1.1211 0.5389
## AgeAccelPheno                      0.1891 0.5148  -0.8200   1.1981 0.7135
## DNAmAgeSkinBloodClockAdjAge        0.3531 0.3786  -0.3889   1.0952 0.3509
## AgeAccelGrim                      -0.2850 0.2825  -0.8387   0.2687 0.3130
## DNAmTLAdjAge                       0.0104 0.0191  -0.0271   0.0478 0.5876
## IEAA                              -0.2151 0.4888  -1.1732   0.7429 0.6598
## EEAA                               0.1109 0.5560  -0.9789   1.2007 0.8419
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05

GEE (No confounders, mutual adjust)

In this section, we perform the generalized estimating equations (GEE) to evaluate the associations between each cluster within current pollutant exposures and each Epigenetic Age Acceleration with the formula: \[ \begin{aligned} Y = & \beta_0 + \beta_1 * X7 + \beta_2 X33 + \beta_3 NkF + \beta_4 NO2 + \beta_5 SO2 \\ & + \epsilon \end{aligned} \] where \(Y\) is one of the epigenetic age accelerations.

Results:

## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."

## The estimated effects:
## $CHLD5_X7
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.1542 0.8714  -1.5538   1.8623 0.8595
## AgeAccelerationResidualHannum      0.1198 0.6817  -1.2162   1.4559 0.8605
## AgeAccelPheno                      0.1160 0.7743  -1.4017   1.6337 0.8809
## DNAmAgeSkinBloodClockAdjAge       -0.2369 0.6866  -1.5826   1.1088 0.7300
## AgeAccelGrim                      -0.1234 0.3872  -0.8824   0.6357 0.7501
## DNAmTLAdjAge                       0.0233 0.0308  -0.0370   0.0835 0.4491
## IEAA                               0.7315 0.7440  -0.7267   2.1897 0.3255
## EEAA                               0.0345 0.9132  -1.7554   1.8245 0.9699
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CHLD5_X33
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.0098 0.7533  -1.4667   1.4863 0.9896
## AgeAccelerationResidualHannum      0.2661 0.5870  -0.8844   1.4167 0.6503
## AgeAccelPheno                      0.8392 0.6226  -0.3811   2.0595 0.1777
## DNAmAgeSkinBloodClockAdjAge        0.6166 0.5482  -0.4579   1.6910 0.2607
## AgeAccelGrim                       0.9502 0.3713   0.2224   1.6779 0.0105
## DNAmTLAdjAge                      -0.0095 0.0260  -0.0604   0.0414 0.7153
## IEAA                              -0.5891 0.6541  -1.8712   0.6929 0.3678
## EEAA                               0.5094 0.7420  -0.9450   1.9638 0.4924
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                    <= 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CHLD5_NkF
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.0302 0.3404  -0.6370   0.6974 0.9292
## AgeAccelerationResidualHannum      0.1769 0.3099  -0.4305   0.7844 0.5681
## AgeAccelPheno                      0.0038 0.3681  -0.7176   0.7252 0.9918
## DNAmAgeSkinBloodClockAdjAge       -0.0150 0.2735  -0.5511   0.5212 0.9564
## AgeAccelGrim                       0.4253 0.2618  -0.0877   0.9384 0.1042
## DNAmTLAdjAge                      -0.0233 0.0184  -0.0594   0.0128 0.2062
## IEAA                              -0.1897 0.3008  -0.7793   0.3999 0.5283
## EEAA                               0.2388 0.4339  -0.6117   1.0892 0.5821
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CHLD5_NO2
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.2186 0.3798  -0.9630   0.5257 0.5648
## AgeAccelerationResidualHannum     -0.0820 0.3754  -0.8178   0.6538 0.8271
## AgeAccelPheno                      0.1281 0.4045  -0.6646   0.9209 0.7514
## DNAmAgeSkinBloodClockAdjAge        0.2933 0.2964  -0.2876   0.8741 0.3224
## AgeAccelGrim                      -0.0826 0.2296  -0.5326   0.3674 0.7190
## DNAmTLAdjAge                      -0.0086 0.0192  -0.0462   0.0291 0.6552
## IEAA                              -0.0313 0.3454  -0.7082   0.6457 0.9278
## EEAA                              -0.1588 0.4849  -1.1092   0.7916 0.7433
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CHLD5_SO2
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.0692 0.7041  -1.4493   1.3109 0.9217
## AgeAccelerationResidualHannum      0.3577 0.6176  -0.8528   1.5682 0.5624
## AgeAccelPheno                      0.0517 0.5713  -1.0679   1.1714 0.9278
## DNAmAgeSkinBloodClockAdjAge        0.0078 0.4361  -0.8470   0.8626 0.9857
## AgeAccelGrim                      -0.3245 0.3228  -0.9573   0.3083 0.3149
## DNAmTLAdjAge                       0.0217 0.0274  -0.0320   0.0754 0.4290
## IEAA                               0.1010 0.6351  -1.1439   1.3458 0.8737
## EEAA                               0.2001 0.7612  -1.2919   1.6920 0.7927
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05

3.3. Clusters based on model-based lifetime exposure estimates (clusCUM6)

The file “LEX_clus CUM6.csv” has information on estimated cumulative pollutant exposures during the lifecourse. Estimates are available for 6 different prototypes (cluster variables) for a total of 161 subjects and 211 visits. The prototypes are labelled as:

CUM6_BC_NO2_PM – a cluster of BC, NO2, and PM
CUM6_PAH36 – a large cluster of 36 PAHs
CUM6_DlP – DlP only
CUM6_NkF – NkF only
CUM6_RET – retene only
CUM6_SO2 – SO2 only

Summary the exposure estimates:

Other
(N=25)
Smoky
(N=87)
Overall
(N=129)
CUM6_BC_NO2_PM
Mean (SD) 0.433 (0.855) -0.0170 (0.999) 0.116 (1.01)
Median (IQR) 0.427 (0.801) 0.0971 (1.78) 0.285 (1.46)
Missing 2 (8.0%) 1 (1.1%) 3 (2.3%)
CUM6_PAH36
Mean (SD) -0.178 (1.04) 0.282 (0.936) 0.196 (0.984)
Median (IQR) -0.472 (1.73) 0.322 (1.71) 0.250 (1.74)
Missing 2 (8.0%) 1 (1.1%) 3 (2.3%)
CUM6_DlP
Mean (SD) 0.626 (0.512) -0.377 (1.06) -0.180 (1.03)
Median (IQR) 0.596 (0.531) -0.661 (1.84) -0.474 (1.76)
Missing 2 (8.0%) 1 (1.1%) 3 (2.3%)
CUM6_NkF
Mean (SD) 0.215 (1.17) -0.114 (1.11) -0.0197 (1.08)
Median (IQR) 0.105 (1.40) -0.312 (1.39) -0.0874 (1.19)
Missing 2 (8.0%) 1 (1.1%) 3 (2.3%)
CUM6_RET
Mean (SD) 0.317 (1.16) -0.273 (0.832) -0.129 (1.03)
Median (IQR) 0.217 (1.67) -0.252 (0.991) -0.220 (1.14)
Missing 2 (8.0%) 1 (1.1%) 3 (2.3%)
CUM6_SO2
Mean (SD) 0.612 (1.01) -0.208 (0.832) -0.0793 (0.950)
Median (IQR) 0.791 (1.35) -0.0285 (1.22) 0.0903 (1.14)
Missing 2 (8.0%) 1 (1.1%) 3 (2.3%)

Primary analysis

GEE (with confounders)

In this section, we perform the generalized estimating equations (GEE) to evaluate the associations between each cluster within current pollutant exposures and each Epigenetic Age Acceleration with the formula: \[ \begin{aligned} Y = & \beta_0 + \beta_1 * X \\ & + \beta_2 * county + \beta_3 * BMI + \beta_4 * ses + \beta_5 * edu + \epsilon \end{aligned} \] where \(Y\) is one of the epigenetic age accelerations and X is one of the cluster estimates.

Results:

## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."

## The estimated effects:
## $CUM6_BC_NO2_PM
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.4786 0.5704  -0.6394   1.5967 0.4014
## AgeAccelerationResidualHannum      0.5152 0.5265  -0.5167   1.5472 0.3278
## AgeAccelPheno                      0.3777 0.5950  -0.7886   1.5439 0.5256
## DNAmAgeSkinBloodClockAdjAge       -0.0071 0.5818  -1.1475   1.1332 0.9902
## AgeAccelGrim                       0.9077 0.3443   0.2329   1.5825 0.0084
## DNAmTLAdjAge                      -0.0240 0.0188  -0.0610   0.0129 0.2024
## IEAA                               0.6290 0.5653  -0.4789   1.7369 0.2658
## EEAA                               0.8229 0.6469  -0.4451   2.0909 0.2034
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                    <= 0.01
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CUM6_PAH36
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.4288 0.5009  -0.5530   1.4106 0.3920
## AgeAccelerationResidualHannum      0.3748 0.4646  -0.5357   1.2854 0.4198
## AgeAccelPheno                      0.8962 0.4748  -0.0345   1.8268 0.0591
## DNAmAgeSkinBloodClockAdjAge        0.5333 0.3895  -0.2302   1.2967 0.1710
## AgeAccelGrim                       1.1373 0.2520   0.6435   1.6312 0.0000
## DNAmTLAdjAge                      -0.0126 0.0181  -0.0481   0.0228 0.4857
## IEAA                               0.3233 0.4790  -0.6156   1.2621 0.4997
## EEAA                               0.5687 0.5557  -0.5205   1.6579 0.3061
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                   <= 0.001
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CUM6_DlP
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.5116 0.4935  -0.4557   1.4789 0.2999
## AgeAccelerationResidualHannum      0.0323 0.4617  -0.8727   0.9372 0.9443
## AgeAccelPheno                     -0.0624 0.4323  -0.9097   0.7849 0.8852
## DNAmAgeSkinBloodClockAdjAge        0.1294 0.3741  -0.6039   0.8627 0.7295
## AgeAccelGrim                      -0.4971 0.2268  -0.9417  -0.0525 0.0284
## DNAmTLAdjAge                      -0.0239 0.0184  -0.0599   0.0121 0.1935
## IEAA                               0.5841 0.4381  -0.2747   1.4428 0.1825
## EEAA                               0.1843 0.5795  -0.9515   1.3201 0.7505
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                    <= 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CUM6_NkF
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.2161 0.3560  -0.4816   0.9139 0.5438
## AgeAccelerationResidualHannum      0.1657 0.3699  -0.5594   0.8907 0.6543
## AgeAccelPheno                     -0.0775 0.4058  -0.8729   0.7179 0.8485
## DNAmAgeSkinBloodClockAdjAge       -0.1047 0.3530  -0.7966   0.5871 0.7667
## AgeAccelGrim                       0.5782 0.2254   0.1364   1.0200 0.0103
## DNAmTLAdjAge                      -0.0380 0.0174  -0.0720  -0.0039 0.0291
## IEAA                               0.1227 0.3111  -0.4870   0.7324 0.6933
## EEAA                               0.2863 0.4888  -0.6718   1.2445 0.5581
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                    <= 0.05
## DNAmTLAdjAge                    <= 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CUM6_RET
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.2691 0.4450  -0.6031   1.1414 0.5453
## AgeAccelerationResidualHannum     -0.0012 0.3568  -0.7005   0.6981 0.9973
## AgeAccelPheno                     -0.1489 0.4803  -1.0903   0.7924 0.7565
## DNAmAgeSkinBloodClockAdjAge       -0.2516 0.4283  -1.0911   0.5878 0.5568
## AgeAccelGrim                       0.4833 0.3252  -0.1542   1.1207 0.1373
## DNAmTLAdjAge                      -0.0054 0.0176  -0.0399   0.0291 0.7594
## IEAA                               0.3880 0.3965  -0.3891   1.1652 0.3277
## EEAA                               0.0425 0.4851  -0.9084   0.9933 0.9303
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CUM6_SO2
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.1809 0.5663  -1.2908   0.9291 0.7494
## AgeAccelerationResidualHannum     -0.0030 0.5637  -1.1078   1.1019 0.9958
## AgeAccelPheno                     -0.4582 0.5884  -1.6115   0.6951 0.4361
## DNAmAgeSkinBloodClockAdjAge        0.0715 0.4785  -0.8664   1.0095 0.8812
## AgeAccelGrim                      -0.4746 0.3137  -1.0894   0.1402 0.1302
## DNAmTLAdjAge                       0.0229 0.0223  -0.0207   0.0666 0.3028
## IEAA                              -0.0673 0.4926  -1.0327   0.8982 0.8914
## EEAA                              -0.2555 0.6815  -1.5912   1.0803 0.7078
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05

GEE (Mix, mutual adjust)

In this section, we perform the generalized estimating equations (GEE) to evaluate the associations between each cluster within current pollutant exposures and each Epigenetic Age Acceleration with the formula: \[ \begin{aligned} Y = & \beta_0 + \beta_1 * BC\_NO2\_PM + \beta_2 PAH36 + \beta_3 DlP + \beta_4 NkF + \beta_5 RET + \beta_6 SO2 \\ & + \beta_7 * county + \beta_8 * BMI + \beta_9 * ses + \beta_10 * edu + \epsilon \end{aligned} \] where \(Y\) is one of the epigenetic age accelerations.

Results:

## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."

## The estimated effects:
## $CUM6_BC_NO2_PM
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.2730 0.6524  -1.5517   1.0057 0.6756
## AgeAccelerationResidualHannum      0.6151 0.7013  -0.7594   1.9896 0.3804
## AgeAccelPheno                     -0.2835 0.8236  -1.8977   1.3307 0.7306
## DNAmAgeSkinBloodClockAdjAge       -0.7631 0.6624  -2.0615   0.5352 0.2493
## AgeAccelGrim                       0.7149 0.4833  -0.2323   1.6622 0.1391
## DNAmTLAdjAge                      -0.0325 0.0281  -0.0876   0.0226 0.2481
## IEAA                              -0.0894 0.6934  -1.4484   1.2696 0.8974
## EEAA                               0.9116 0.8688  -0.7913   2.6144 0.2941
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CUM6_PAH36
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.9323 0.6682  -0.3774   2.2420 0.1630
## AgeAccelerationResidualHannum      0.1279 0.6700  -1.1853   1.4410 0.8486
## AgeAccelPheno                      1.5842 0.7983   0.0196   3.1489 0.0472
## DNAmAgeSkinBloodClockAdjAge        1.4449 0.6380   0.1944   2.6953 0.0235
## AgeAccelGrim                       0.5238 0.4610  -0.3797   1.4273 0.2558
## DNAmTLAdjAge                       0.0023 0.0288  -0.0542   0.0589 0.9355
## IEAA                               0.7026 0.6603  -0.5916   1.9967 0.2873
## EEAA                               0.2849 0.8493  -1.3797   1.9496 0.7373
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                   <= 0.05
## DNAmAgeSkinBloodClockAdjAge     <= 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CUM6_DlP
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            1.1621 0.6226  -0.0581   2.3824 0.0620
## AgeAccelerationResidualHannum     -0.1086 0.5988  -1.2823   1.0652 0.8561
## AgeAccelPheno                      0.7049 0.5797  -0.4313   1.8410 0.2240
## DNAmAgeSkinBloodClockAdjAge        0.8192 0.5197  -0.1995   1.8378 0.1150
## AgeAccelGrim                      -0.5787 0.3413  -1.2476   0.0902 0.0899
## DNAmTLAdjAge                      -0.0074 0.0256  -0.0576   0.0428 0.7720
## IEAA                               1.2352 0.5457   0.1657   2.3048 0.0236
## EEAA                               0.1156 0.7762  -1.4057   1.6369 0.8816
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                            <= 0.05
## EEAA                             > 0.05
## 
## $CUM6_NkF
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.4062 0.4337  -1.2563   0.4439 0.3490
## AgeAccelerationResidualHannum      0.2405 0.3949  -0.5336   1.0146 0.5426
## AgeAccelPheno                     -0.3634 0.4882  -1.3203   0.5934 0.4566
## DNAmAgeSkinBloodClockAdjAge       -0.4152 0.4260  -1.2502   0.4199 0.3298
## AgeAccelGrim                       0.6814 0.2909   0.1113   1.2515 0.0191
## DNAmTLAdjAge                      -0.0433 0.0209  -0.0842  -0.0024 0.0379
## IEAA                              -0.6019 0.3794  -1.3455   0.1416 0.1126
## EEAA                               0.2872 0.5563  -0.8031   1.3775 0.6056
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                    <= 0.05
## DNAmTLAdjAge                    <= 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CUM6_RET
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.3670 0.6210  -0.8501   1.5841 0.5545
## AgeAccelerationResidualHannum     -0.4159 0.5437  -1.4815   0.6497 0.4443
## AgeAccelPheno                     -0.4622 0.5574  -1.5547   0.6302 0.4069
## DNAmAgeSkinBloodClockAdjAge       -0.1741 0.5141  -1.1818   0.8336 0.7348
## AgeAccelGrim                      -0.4531 0.4344  -1.3044   0.3983 0.2969
## DNAmTLAdjAge                       0.0305 0.0221  -0.0128   0.0739 0.1674
## IEAA                               0.6335 0.5167  -0.3791   1.6462 0.2201
## EEAA                              -0.5941 0.7039  -1.9737   0.7855 0.3986
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CUM6_SO2
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.2686 0.5881  -1.4213   0.8841 0.6479
## AgeAccelerationResidualHannum     -0.0950 0.6022  -1.2752   1.0852 0.8747
## AgeAccelPheno                     -0.6224 0.5838  -1.7667   0.5219 0.2864
## DNAmAgeSkinBloodClockAdjAge       -0.0324 0.4924  -0.9976   0.9327 0.9475
## AgeAccelGrim                      -0.3984 0.3069  -0.9999   0.2031 0.1942
## DNAmTLAdjAge                       0.0335 0.0231  -0.0119   0.0789 0.1477
## IEAA                              -0.1197 0.4982  -1.0961   0.8566 0.8100
## EEAA                              -0.4561 0.7410  -1.9085   0.9962 0.5382
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05

Sensitivity analyses

GEE (No confounders)

In this section, we perform the generalized estimating equations (GEE) to evaluate the associations between each cluster within current pollutant exposures and each Epigenetic Age Acceleration with the formula: \[ \begin{aligned} Y = & \beta_0 + \beta_1 * X + \epsilon \end{aligned} \] where \(Y\) is one of the epigenetic age accelerations and X is one of the cluster estimates.

Results:

## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."

## The estimated effects:
## $CUM6_BC_NO2_PM
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.1884 0.3968  -0.9660   0.5893 0.6350
## AgeAccelerationResidualHannum      0.3993 0.3004  -0.1895   0.9880 0.1838
## AgeAccelPheno                      0.5024 0.4156  -0.3122   1.3170 0.2267
## DNAmAgeSkinBloodClockAdjAge       -0.0883 0.3483  -0.7710   0.5943 0.7997
## AgeAccelGrim                       0.5445 0.2453   0.0638   1.0252 0.0264
## DNAmTLAdjAge                      -0.0227 0.0166  -0.0554   0.0099 0.1718
## IEAA                               0.1498 0.3613  -0.5583   0.8579 0.6784
## EEAA                               0.4604 0.4025  -0.3284   1.2493 0.2526
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                    <= 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CUM6_PAH36
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.0036 0.4229  -0.8324   0.8252 0.9932
## AgeAccelerationResidualHannum      0.3575 0.3682  -0.3641   1.0791 0.3315
## AgeAccelPheno                      0.8447 0.3868   0.0865   1.6029 0.0290
## DNAmAgeSkinBloodClockAdjAge        0.3168 0.3249  -0.3201   0.9537 0.3296
## AgeAccelGrim                       0.8579 0.2642   0.3401   1.3757 0.0012
## DNAmTLAdjAge                      -0.0123 0.0159  -0.0434   0.0188 0.4376
## IEAA                               0.0988 0.4034  -0.6919   0.8895 0.8065
## EEAA                               0.4204 0.4479  -0.4575   1.2982 0.3480
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                   <= 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                    <= 0.01
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CUM6_DlP
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.2182 0.4332  -0.6308   1.0672 0.6145
## AgeAccelerationResidualHannum      0.0243 0.3848  -0.7300   0.7786 0.9496
## AgeAccelPheno                      0.2035 0.3663  -0.5145   0.9214 0.5786
## DNAmAgeSkinBloodClockAdjAge        0.1096 0.2981  -0.4746   0.6938 0.7131
## AgeAccelGrim                      -0.1918 0.2177  -0.6185   0.2350 0.3785
## DNAmTLAdjAge                      -0.0277 0.0138  -0.0548  -0.0006 0.0450
## IEAA                               0.4099 0.3883  -0.3512   1.1710 0.2912
## EEAA                               0.0564 0.4831  -0.8904   1.0032 0.9071
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                    <= 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CUM6_NkF
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.0429 0.3555  -0.6537   0.7396 0.9039
## AgeAccelerationResidualHannum      0.1869 0.3603  -0.5193   0.8932 0.6039
## AgeAccelPheno                      0.1030 0.3965  -0.6740   0.8801 0.7949
## DNAmAgeSkinBloodClockAdjAge       -0.1298 0.3189  -0.7549   0.4952 0.6839
## AgeAccelGrim                       0.5998 0.2254   0.1580   1.0415 0.0078
## DNAmTLAdjAge                      -0.0396 0.0149  -0.0688  -0.0104 0.0079
## IEAA                               0.0726 0.3010  -0.5174   0.6626 0.8094
## EEAA                               0.2414 0.4768  -0.6932   1.1760 0.6127
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                    <= 0.01
## DNAmTLAdjAge                    <= 0.01
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CUM6_RET
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.0873 0.4603  -0.8148   0.9894 0.8495
## AgeAccelerationResidualHannum      0.0181 0.3516  -0.6711   0.7072 0.9590
## AgeAccelPheno                     -0.0092 0.4657  -0.9219   0.9035 0.9843
## DNAmAgeSkinBloodClockAdjAge       -0.2701 0.4132  -1.0799   0.5398 0.5134
## AgeAccelGrim                       0.5156 0.3173  -0.1064   1.1376 0.1042
## DNAmTLAdjAge                      -0.0093 0.0174  -0.0434   0.0247 0.5909
## IEAA                               0.3182 0.3985  -0.4627   1.0992 0.4245
## EEAA                              -0.0022 0.4759  -0.9350   0.9306 0.9963
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CUM6_SO2
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.5367 0.4805  -1.4785   0.4050 0.2639
## AgeAccelerationResidualHannum      0.0624 0.4131  -0.7471   0.8720 0.8798
## AgeAccelPheno                     -0.0746 0.5017  -1.0579   0.9086 0.8817
## DNAmAgeSkinBloodClockAdjAge        0.0566 0.3702  -0.6689   0.7822 0.8784
## AgeAccelGrim                      -0.3999 0.2539  -0.8976   0.0978 0.1153
## DNAmTLAdjAge                       0.0096 0.0177  -0.0252   0.0443 0.5893
## IEAA                              -0.2477 0.4356  -1.1015   0.6060 0.5696
## EEAA                              -0.2363 0.4984  -1.2132   0.7407 0.6355
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05

GEE (No confounders, mutual adjust)

In this section, we perform the generalized estimating equations (GEE) to evaluate the associations between each cluster within current pollutant exposures and each Epigenetic Age Acceleration with the formula: \[ \begin{aligned} Y = & \beta_0 + \beta_1 * BC\_NO2\_PM + \beta_2 PAH36 + \beta_3 DlP + \beta_4 NkF + \beta_5 RET + \beta_6 SO2 \\ & + \epsilon \end{aligned} \] where \(Y\) is one of the epigenetic age accelerations.

Results:

## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."

## The estimated effects:
## $CUM6_BC_NO2_PM
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.7127 0.5955  -1.8800   0.4545 0.2314
## AgeAccelerationResidualHannum      0.6054 0.5958  -0.5623   1.7732 0.3095
## AgeAccelPheno                     -0.2482 0.8394  -1.8934   1.3970 0.7675
## DNAmAgeSkinBloodClockAdjAge       -0.8953 0.6236  -2.1175   0.3269 0.1511
## AgeAccelGrim                       0.3240 0.4702  -0.5976   1.2455 0.4908
## DNAmTLAdjAge                      -0.0300 0.0296  -0.0880   0.0281 0.3115
## IEAA                              -0.4600 0.5869  -1.6104   0.6904 0.4332
## EEAA                               0.8186 0.8015  -0.7523   2.3894 0.3071
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CUM6_PAH36
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.7815 0.6724  -0.5364   2.0995 0.2451
## AgeAccelerationResidualHannum      0.0064 0.6754  -1.3173   1.3301 0.9925
## AgeAccelPheno                      1.6047 0.8088   0.0195   3.1900 0.0472
## DNAmAgeSkinBloodClockAdjAge        1.3850 0.6435   0.1237   2.6464 0.0314
## AgeAccelGrim                       0.5224 0.4881  -0.4342   1.4790 0.2845
## DNAmTLAdjAge                       0.0043 0.0277  -0.0501   0.0587 0.8768
## IEAA                               0.6628 0.6674  -0.6452   1.9709 0.3206
## EEAA                               0.0605 0.8465  -1.5987   1.7196 0.9431
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                   <= 0.05
## DNAmAgeSkinBloodClockAdjAge     <= 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CUM6_DlP
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.9648 0.6171  -0.2447   2.1744 0.1179
## AgeAccelerationResidualHannum     -0.2146 0.5478  -1.2884   0.8591 0.6952
## AgeAccelPheno                      0.9482 0.5944  -0.2169   2.1132 0.1107
## DNAmAgeSkinBloodClockAdjAge        0.8418 0.5075  -0.1530   1.8366 0.0972
## AgeAccelGrim                      -0.2335 0.3869  -0.9918   0.5248 0.5461
## DNAmTLAdjAge                      -0.0109 0.0229  -0.0559   0.0340 0.6333
## IEAA                               1.1205 0.5518   0.0391   2.2020 0.0423
## EEAA                              -0.1084 0.7307  -1.5407   1.3238 0.8820
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                            <= 0.05
## EEAA                             > 0.05
## 
## $CUM6_NkF
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.3678 0.4506  -1.2509   0.5153 0.4143
## AgeAccelerationResidualHannum      0.2938 0.4300  -0.5489   1.1365 0.4944
## AgeAccelPheno                     -0.3958 0.4946  -1.3651   0.5735 0.4235
## DNAmAgeSkinBloodClockAdjAge       -0.4530 0.4363  -1.3082   0.4022 0.2992
## AgeAccelGrim                       0.6049 0.3250  -0.0322   1.2420 0.0627
## DNAmTLAdjAge                      -0.0426 0.0207  -0.0832  -0.0020 0.0399
## IEAA                              -0.6206 0.3863  -1.3776   0.1365 0.1081
## EEAA                               0.3705 0.5999  -0.8053   1.5462 0.5369
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                    <= 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CUM6_RET
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.3001 0.6469  -0.9677   1.5680 0.6427
## AgeAccelerationResidualHannum     -0.4716 0.5510  -1.5515   0.6084 0.3921
## AgeAccelPheno                     -0.3517 0.5555  -1.4406   0.7371 0.5267
## DNAmAgeSkinBloodClockAdjAge       -0.1332 0.5120  -1.1367   0.8703 0.7947
## AgeAccelGrim                      -0.2467 0.4382  -1.1057   0.6123 0.5735
## DNAmTLAdjAge                       0.0283 0.0216  -0.0140   0.0707 0.1901
## IEAA                               0.6105 0.5223  -0.4132   1.6343 0.2424
## EEAA                              -0.6961 0.7125  -2.0925   0.7004 0.3286
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $CUM6_SO2
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.6641 0.5296  -1.7021   0.3738 0.2098
## AgeAccelerationResidualHannum     -0.1502 0.5194  -1.1682   0.8679 0.7725
## AgeAccelPheno                     -0.4912 0.5618  -1.5924   0.6101 0.3820
## DNAmAgeSkinBloodClockAdjAge       -0.0404 0.4557  -0.9336   0.8529 0.9294
## AgeAccelGrim                      -0.5686 0.2749  -1.1073  -0.0298 0.0386
## DNAmTLAdjAge                       0.0325 0.0206  -0.0079   0.0730 0.1151
## IEAA                              -0.4426 0.4453  -1.3154   0.4302 0.3202
## EEAA                              -0.6035 0.6288  -1.8360   0.6290 0.3372
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                    <= 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05

3.0. All plots together

3.4. Clusters based on pollutant measurements (clusMEAS6)

The file “LEX_clusMEAS6.csv” has information on measured pollutant exposures during each visit. Estimates are available for 6 different prototypes (cluster variables) for a total of 54 subjects and 54 visits. The prototypes are labelled as:

MEAS6_BC_ PM_RET – a cluster of BC, PM, and retene
MEAS6_X31 – a large cluster of 31 air pollutants
MEAS6_X5 – a smaller cluster of 5 air pollutants
MEAS6_DlP – DlP only
MEAS6_NkF – NkF only
MEAS6_ NO2_SO2 – NO2, and SO2

Summary the exposure estimates:

Other
(N=25)
Smoky
(N=87)
Overall
(N=129)
MEAS6_BC_PM_RET
Mean (SD) -0.301 (1.51) 0.0548 (0.649) -0.0510 (1.05)
Median (IQR) -0.303 (1.44) 0.0566 (1.19) -0.110 (1.13)
Missing 4 (16.0%) 48 (55.2%) 64 (49.6%)
MEAS6_X31
Mean (SD) -0.702 (1.12) 0.341 (1.03) -0.00398 (1.13)
Median (IQR) -0.945 (1.42) 0.289 (0.879) 0.141 (1.44)
Missing 4 (16.0%) 48 (55.2%) 64 (49.6%)
MEAS6_X5
Mean (SD) -0.555 (0.809) 0.273 (1.05) 0.0138 (1.02)
Median (IQR) -1.04 (0.550) 0.646 (1.94) -0.104 (2.03)
Missing 4 (16.0%) 48 (55.2%) 64 (49.6%)
MEAS6_DlP
Mean (SD) 0.260 (0.906) -0.0314 (1.07) 0.0186 (0.998)
Median (IQR) 0.348 (1.78) -0.692 (2.24) -0.626 (2.02)
Missing 4 (16.0%) 48 (55.2%) 64 (49.6%)
MEAS6_NkF
Mean (SD) 0.0323 (1.02) -0.0420 (1.01) 0.00920 (1.02)
Median (IQR) -0.389 (0.805) -0.506 (0.973) -0.499 (1.57)
Missing 4 (16.0%) 48 (55.2%) 64 (49.6%)
MEAS6_NO2_SO2
Mean (SD) 0.692 (1.12) -0.159 (0.915) 0.0937 (1.04)
Median (IQR) 0.670 (1.43) -0.430 (1.66) -0.0382 (1.77)
Missing 4 (16.0%) 48 (55.2%) 64 (49.6%)

Primary analysis

GEE (with confounders)

In this section, we perform the generalized estimating equations (GEE) to evaluate the associations between each cluster within current pollutant exposures and each Epigenetic Age Acceleration with the formula: \[ \begin{aligned} Y = & \beta_0 + \beta_1 * X \\ & + \beta_2 * county + \beta_3 * BMI + \beta_4 * ses + \beta_5 * edu + \epsilon \end{aligned} \] where \(Y\) is one of the epigenetic age accelerations and X is one of the cluster estimates.

Results:

## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."

## The estimated effects:
## $MEAS6_BC_PM_RET
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.2131 0.4434  -1.0821   0.6558 0.6307
## AgeAccelerationResidualHannum     -0.3690 0.4019  -1.1567   0.4188 0.3586
## AgeAccelPheno                      0.2287 0.7026  -1.1483   1.6058 0.7447
## DNAmAgeSkinBloodClockAdjAge       -0.0268 0.3873  -0.7859   0.7324 0.9449
## AgeAccelGrim                       0.6926 0.4739  -0.2362   1.6214 0.1439
## DNAmTLAdjAge                      -0.0015 0.0295  -0.0594   0.0564 0.9606
## IEAA                              -0.4851 0.3891  -1.2478   0.2776 0.2126
## EEAA                              -0.4596 0.4796  -1.3996   0.4804 0.3379
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $MEAS6_X31
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            1.0372 0.5907  -0.1207   2.1950 0.0791
## AgeAccelerationResidualHannum      0.7603 0.5751  -0.3669   1.8876 0.1862
## AgeAccelPheno                      1.3384 0.6067   0.1493   2.5275 0.0274
## DNAmAgeSkinBloodClockAdjAge        1.2287 0.5097   0.2297   2.2276 0.0159
## AgeAccelGrim                       1.1050 0.3110   0.4953   1.7146 0.0004
## DNAmTLAdjAge                      -0.0265 0.0240  -0.0735   0.0205 0.2690
## IEAA                               0.4088 0.4659  -0.5043   1.3220 0.3802
## EEAA                               0.9734 0.6286  -0.2587   2.2055 0.1215
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                   <= 0.05
## DNAmAgeSkinBloodClockAdjAge     <= 0.05
## AgeAccelGrim                   <= 0.001
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $MEAS6_X5
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.1163 0.6791  -1.4475   1.2148 0.8640
## AgeAccelerationResidualHannum     -0.6886 0.7466  -2.1520   0.7747 0.3564
## AgeAccelPheno                      0.5990 0.7070  -0.7866   1.9847 0.3968
## DNAmAgeSkinBloodClockAdjAge        0.6521 0.5849  -0.4942   1.7985 0.2648
## AgeAccelGrim                       1.0605 0.3884   0.2992   1.8218 0.0063
## DNAmTLAdjAge                       0.0259 0.0289  -0.0308   0.0826 0.3707
## IEAA                               0.1573 0.5446  -0.9100   1.2247 0.7726
## EEAA                              -1.0902 0.8962  -2.8467   0.6663 0.2238
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                    <= 0.01
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $MEAS6_DlP
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.3307 0.7517  -1.1427   1.8041 0.6600
## AgeAccelerationResidualHannum      0.1404 0.6613  -1.1558   1.4366 0.8319
## AgeAccelPheno                      0.3856 0.7079  -1.0019   1.7731 0.5859
## DNAmAgeSkinBloodClockAdjAge       -0.8663 0.5664  -1.9765   0.2440 0.1262
## AgeAccelGrim                      -0.2806 0.5080  -1.2763   0.7150 0.5806
## DNAmTLAdjAge                      -0.0294 0.0330  -0.0941   0.0354 0.3738
## IEAA                               0.3886 0.5756  -0.7396   1.5168 0.4996
## EEAA                               0.1581 0.8367  -1.4817   1.7980 0.8501
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $MEAS6_NkF
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.1099 0.6676  -1.1987   1.4185 0.8693
## AgeAccelerationResidualHannum      0.6275 0.5196  -0.3909   1.6458 0.2272
## AgeAccelPheno                      0.2914 0.7025  -1.0855   1.6683 0.6783
## DNAmAgeSkinBloodClockAdjAge        0.2283 0.5030  -0.7576   1.2142 0.6499
## AgeAccelGrim                      -0.1056 0.3829  -0.8560   0.6448 0.7826
## DNAmTLAdjAge                      -0.0091 0.0259  -0.0598   0.0417 0.7259
## IEAA                              -0.2750 0.5928  -1.4369   0.8870 0.6428
## EEAA                               0.9232 0.7028  -0.4542   2.3007 0.1890
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $MEAS6_NO2_SO2
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.1663 0.5685  -1.2806   0.9479 0.7698
## AgeAccelerationResidualHannum      0.6345 0.5420  -0.4278   1.6967 0.2417
## AgeAccelPheno                     -0.0485 0.5306  -1.0885   0.9915 0.9271
## DNAmAgeSkinBloodClockAdjAge       -0.1171 0.3961  -0.8934   0.6593 0.7676
## AgeAccelGrim                      -0.3701 0.4232  -1.1996   0.4593 0.3818
## DNAmTLAdjAge                      -0.0228 0.0338  -0.0890   0.0433 0.4988
## IEAA                              -0.2743 0.4718  -1.1990   0.6505 0.5611
## EEAA                               0.3185 0.6518  -0.9591   1.5960 0.6251
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05

GEE (Mix, mutual adjust)

In this section, we perform the generalized estimating equations (GEE) to evaluate the associations between each cluster within current pollutant exposures and each Epigenetic Age Acceleration with the formula: \[ \begin{aligned} Y = & \beta_0 + \beta_1 * BC\_PAH6 + \beta_2 PAH31 + \beta_3 NkF + \beta_4 PM\_RET + \beta_5 NO2 + \beta_6 SO2 \\ & + \beta_7 * county + \beta_8 * BMI + \beta_9 * ses + \beta_10 * edu + \epsilon \end{aligned} \] where \(Y\) is one of the epigenetic age accelerations.

Results:

## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."

## The estimated effects:
## $MEAS6_BC_PM_RET
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.8052 0.7632  -2.3010   0.6906 0.2914
## AgeAccelerationResidualHannum     -0.7006 0.5989  -1.8745   0.4733 0.2421
## AgeAccelPheno                     -0.6131 0.9323  -2.4405   1.2142 0.5108
## DNAmAgeSkinBloodClockAdjAge       -0.9711 0.6184  -2.1831   0.2410 0.1163
## AgeAccelGrim                       0.0925 0.6425  -1.1667   1.3518 0.8855
## DNAmTLAdjAge                      -0.0012 0.0320  -0.0640   0.0617 0.9712
## IEAA                              -0.9818 0.6638  -2.2829   0.3193 0.1392
## EEAA                              -0.8869 0.6880  -2.2353   0.4615 0.1973
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $MEAS6_X31
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            2.5915 1.0286   0.5754   4.6075 0.0118
## AgeAccelerationResidualHannum      2.3493 0.6263   1.1217   3.5769 0.0002
## AgeAccelPheno                      1.9240 0.9541   0.0540   3.7941 0.0437
## DNAmAgeSkinBloodClockAdjAge        2.3571 0.6772   1.0299   3.6844 0.0005
## AgeAccelGrim                       1.1725 0.5775   0.0405   2.3044 0.0423
## DNAmTLAdjAge                      -0.0840 0.0386  -0.1596  -0.0084 0.0293
## IEAA                               1.1612 0.8849  -0.5732   2.8955 0.1894
## EEAA                               3.2309 0.8370   1.5904   4.8715 0.0001
##                               sig_level
## AgeAccelerationResidual         <= 0.05
## AgeAccelerationResidualHannum  <= 0.001
## AgeAccelPheno                   <= 0.05
## DNAmAgeSkinBloodClockAdjAge    <= 0.001
## AgeAccelGrim                    <= 0.05
## DNAmTLAdjAge                    <= 0.05
## IEAA                             > 0.05
## EEAA                           <= 0.001
## 
## $MEAS6_X5
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -1.7309 1.1968  -4.0767   0.6150 0.1481
## AgeAccelerationResidualHannum     -1.9693 1.1237  -4.1717   0.2332 0.0797
## AgeAccelPheno                     -0.4652 1.0716  -2.5655   1.6352 0.6642
## DNAmAgeSkinBloodClockAdjAge       -0.7981 0.8475  -2.4593   0.8630 0.3463
## AgeAccelGrim                      -0.0180 0.8073  -1.6003   1.5644 0.9822
## DNAmTLAdjAge                       0.0877 0.0460  -0.0024   0.1778 0.0564
## IEAA                              -0.2995 1.0465  -2.3506   1.7516 0.7747
## EEAA                              -2.9864 1.3631  -5.6580  -0.3147 0.0285
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                            <= 0.05
## 
## $MEAS6_DlP
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.2058 0.7052  -1.5881   1.1764 0.7704
## AgeAccelerationResidualHannum     -0.4345 0.5723  -1.5562   0.6871 0.4477
## AgeAccelPheno                      0.1030 0.6246  -1.1212   1.3272 0.8690
## DNAmAgeSkinBloodClockAdjAge       -1.2570 0.5106  -2.2577  -0.2562 0.0138
## AgeAccelGrim                      -0.3899 0.4144  -1.2022   0.4225 0.3469
## DNAmTLAdjAge                      -0.0106 0.0251  -0.0599   0.0387 0.6741
## IEAA                               0.2093 0.6092  -0.9847   1.4033 0.7311
## EEAA                              -0.6479 0.6782  -1.9773   0.6815 0.3394
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge     <= 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $MEAS6_NkF
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.7312 0.7189  -2.1402   0.6778 0.3091
## AgeAccelerationResidualHannum     -0.0519 0.6828  -1.3902   1.2864 0.9394
## AgeAccelPheno                     -0.1264 0.7417  -1.5801   1.3274 0.8647
## DNAmAgeSkinBloodClockAdjAge       -0.3063 0.5391  -1.3630   0.7504 0.5699
## AgeAccelGrim                      -0.4543 0.5249  -1.4831   0.5745 0.3868
## DNAmTLAdjAge                       0.0235 0.0309  -0.0372   0.0841 0.4479
## IEAA                              -0.5339 0.7324  -1.9695   0.9016 0.4660
## EEAA                              -0.1986 0.8403  -1.8455   1.4484 0.8132
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $MEAS6_NO2_SO2
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.2723 0.5813  -1.4116   0.8670 0.6394
## AgeAccelerationResidualHannum      0.6689 0.5030  -0.3171   1.6549 0.1836
## AgeAccelPheno                      0.0393 0.5672  -1.0725   1.1510 0.9448
## DNAmAgeSkinBloodClockAdjAge       -0.0496 0.4552  -0.9419   0.8426 0.9132
## AgeAccelGrim                      -0.2664 0.4393  -1.1274   0.5947 0.5443
## DNAmTLAdjAge                      -0.0335 0.0332  -0.0985   0.0315 0.3121
## IEAA                              -0.4687 0.4682  -1.3863   0.4490 0.3168
## EEAA                               0.3302 0.5877  -0.8216   1.4821 0.5742
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05

Sensitivity analyses

GEE (no confounders)

In this section, we perform the generalized estimating equations (GEE) to evaluate the associations between each cluster within current pollutant exposures and each Epigenetic Age Acceleration with the formula: \[ \begin{aligned} Y = & \beta_0 + \beta_1 * X + \epsilon \end{aligned} \] where \(Y\) is one of the epigenetic age accelerations and X is one of the cluster estimates.

Results:

## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."

## The estimated effects:
## $MEAS6_BC_PM_RET
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.2167 0.4383  -1.0758   0.6423 0.6209
## AgeAccelerationResidualHannum     -0.4474 0.4061  -1.2434   0.3485 0.2705
## AgeAccelPheno                      0.1582 0.6700  -1.1550   1.4713 0.8134
## DNAmAgeSkinBloodClockAdjAge       -0.1368 0.3571  -0.8366   0.5630 0.7017
## AgeAccelGrim                       0.6923 0.4524  -0.1944   1.5791 0.1260
## DNAmTLAdjAge                       0.0073 0.0293  -0.0503   0.0648 0.8047
## IEAA                              -0.3835 0.3918  -1.1513   0.3844 0.3276
## EEAA                              -0.6213 0.5111  -1.6231   0.3804 0.2241
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $MEAS6_X31
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            1.0149 0.6577  -0.2742   2.3040 0.1228
## AgeAccelerationResidualHannum      0.6948 0.6320  -0.5440   1.9336 0.2716
## AgeAccelPheno                      1.1231 0.5958  -0.0447   2.2909 0.0594
## DNAmAgeSkinBloodClockAdjAge        1.0622 0.5431  -0.0022   2.1266 0.0505
## AgeAccelGrim                       1.0435 0.3271   0.4024   1.6847 0.0014
## DNAmTLAdjAge                      -0.0187 0.0252  -0.0681   0.0307 0.4589
## IEAA                               0.4805 0.4937  -0.4872   1.4482 0.3304
## EEAA                               0.8324 0.7485  -0.6347   2.2996 0.2661
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                    <= 0.01
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $MEAS6_X5
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.3006 0.6067  -1.4897   0.8885 0.6202
## AgeAccelerationResidualHannum     -0.8748 0.5914  -2.0339   0.2843 0.1391
## AgeAccelPheno                      0.3478 0.5754  -0.7799   1.4755 0.5455
## DNAmAgeSkinBloodClockAdjAge        0.2598 0.5129  -0.7455   1.2651 0.6125
## AgeAccelGrim                       0.7729 0.3759   0.0362   1.5096 0.0397
## DNAmTLAdjAge                       0.0403 0.0248  -0.0083   0.0888 0.1041
## IEAA                               0.2191 0.4639  -0.6901   1.1283 0.6367
## EEAA                              -1.4382 0.7134  -2.8365  -0.0399 0.0438
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                    <= 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                            <= 0.05
## 
## $MEAS6_DlP
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.4196 0.6529  -0.8601   1.6994 0.5204
## AgeAccelerationResidualHannum      0.2971 0.6100  -0.8984   1.4926 0.6262
## AgeAccelPheno                      0.4584 0.6170  -0.7510   1.6678 0.4575
## DNAmAgeSkinBloodClockAdjAge       -0.5615 0.5524  -1.6442   0.5212 0.3094
## AgeAccelGrim                      -0.1811 0.5272  -1.2143   0.8522 0.7312
## DNAmTLAdjAge                      -0.0384 0.0304  -0.0980   0.0212 0.2066
## IEAA                               0.2697 0.4931  -0.6966   1.2361 0.5843
## EEAA                               0.4537 0.7754  -1.0662   1.9736 0.5585
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $MEAS6_NkF
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.2503 0.7174  -1.1558   1.6564 0.7272
## AgeAccelerationResidualHannum      0.7301 0.5467  -0.3414   1.8017 0.1817
## AgeAccelPheno                      0.2821 0.6799  -1.0505   1.6147 0.6782
## DNAmAgeSkinBloodClockAdjAge        0.2450 0.5915  -0.9144   1.4044 0.6787
## AgeAccelGrim                       0.0144 0.4106  -0.7904   0.8192 0.9720
## DNAmTLAdjAge                      -0.0127 0.0251  -0.0619   0.0364 0.6120
## IEAA                              -0.2325 0.6420  -1.4908   1.0258 0.7172
## EEAA                               1.0794 0.7402  -0.3713   2.5301 0.1447
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $MEAS6_NO2_SO2
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.2145 0.6073  -0.9757   1.4047 0.7239
## AgeAccelerationResidualHannum      0.7399 0.5173  -0.2741   1.7538 0.1527
## AgeAccelPheno                      0.1041 0.5513  -0.9765   1.1847 0.8502
## DNAmAgeSkinBloodClockAdjAge        0.3653 0.4951  -0.6050   1.3357 0.4606
## AgeAccelGrim                      -0.0571 0.3785  -0.7991   0.6848 0.8801
## DNAmTLAdjAge                      -0.0276 0.0268  -0.0802   0.0249 0.3022
## IEAA                               0.1130 0.5503  -0.9656   1.1916 0.8373
## EEAA                               0.5420 0.6373  -0.7071   1.7911 0.3950
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05

GEE (Mix, mutual adjust)

In this section, we perform the generalized estimating equations (GEE) to evaluate the associations between each cluster within current pollutant exposures and each Epigenetic Age Acceleration with the formula: \[ \begin{aligned} Y = & \beta_0 + \beta_1 * BC\_PAH6 + \beta_2 PAH31 + \beta_3 NkF + \beta_4 PM\_RET + \beta_5 NO2 + \beta_6 SO2 \\ & + \beta_7 * county + \beta_8 * BMI + \beta_9 * ses + \beta_10 * edu + \epsilon \end{aligned} \] where \(Y\) is one of the epigenetic age accelerations.

Results:

## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."
## [1] "Fitting with 65 observations."

## The estimated effects:
## $MEAS6_BC_PM_RET
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.7407 0.7753  -2.2603   0.7790 0.3394
## AgeAccelerationResidualHannum     -0.6831 0.6184  -1.8951   0.5289 0.2693
## AgeAccelPheno                     -0.6034 0.9533  -2.4718   1.2651 0.5268
## DNAmAgeSkinBloodClockAdjAge       -0.8952 0.5949  -2.0611   0.2708 0.1324
## AgeAccelGrim                       0.1771 0.6602  -1.1170   1.4712 0.7885
## DNAmTLAdjAge                      -0.0018 0.0347  -0.0699   0.0663 0.9594
## IEAA                              -0.9163 0.6674  -2.2245   0.3919 0.1698
## EEAA                              -0.8543 0.7222  -2.2699   0.5613 0.2369
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $MEAS6_X31
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            2.5894 1.0393   0.5523   4.6265 0.0127
## AgeAccelerationResidualHannum      2.2527 0.6493   0.9801   3.5253 0.0005
## AgeAccelPheno                      1.6932 0.9645  -0.1972   3.5836 0.0792
## DNAmAgeSkinBloodClockAdjAge        2.2402 0.6968   0.8744   3.6059 0.0013
## AgeAccelGrim                       1.1844 0.5342   0.1375   2.2313 0.0266
## DNAmTLAdjAge                      -0.0791 0.0338  -0.1454  -0.0129 0.0192
## IEAA                               1.1619 0.9394  -0.6793   3.0031 0.2161
## EEAA                               3.1071 0.8293   1.4817   4.7326 0.0002
##                               sig_level
## AgeAccelerationResidual         <= 0.05
## AgeAccelerationResidualHannum  <= 0.001
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge     <= 0.01
## AgeAccelGrim                    <= 0.05
## DNAmTLAdjAge                    <= 0.05
## IEAA                             > 0.05
## EEAA                           <= 0.001
## 
## $MEAS6_X5
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -1.7267 1.1445  -3.9699   0.5165 0.1314
## AgeAccelerationResidualHannum     -1.9205 0.9412  -3.7652  -0.0758 0.0413
## AgeAccelPheno                     -0.3795 0.9556  -2.2525   1.4935 0.6913
## DNAmAgeSkinBloodClockAdjAge       -0.9976 0.8396  -2.6432   0.6479 0.2347
## AgeAccelGrim                      -0.2187 0.8025  -1.7916   1.3542 0.7852
## DNAmTLAdjAge                       0.0897 0.0389   0.0135   0.1659 0.0210
## IEAA                              -0.1290 1.0229  -2.1339   1.8758 0.8996
## EEAA                              -3.0352 1.1266  -5.2433  -0.8271 0.0071
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum   <= 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                    <= 0.05
## IEAA                             > 0.05
## EEAA                            <= 0.01
## 
## $MEAS6_DlP
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.1338 0.6936  -1.4932   1.2256 0.8470
## AgeAccelerationResidualHannum     -0.3661 0.5512  -1.4464   0.7143 0.5066
## AgeAccelPheno                      0.3079 0.5690  -0.8074   1.4232 0.5885
## DNAmAgeSkinBloodClockAdjAge       -0.9609 0.5164  -1.9730   0.0512 0.0628
## AgeAccelGrim                      -0.2218 0.4382  -1.0806   0.6370 0.6128
## DNAmTLAdjAge                      -0.0129 0.0233  -0.0585   0.0327 0.5796
## IEAA                               0.1340 0.5884  -1.0194   1.2873 0.8199
## EEAA                              -0.4883 0.6544  -1.7710   0.7943 0.4555
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $MEAS6_NkF
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.6478 0.7652  -2.1477   0.8520 0.3972
## AgeAccelerationResidualHannum     -0.0370 0.6745  -1.3589   1.2850 0.9563
## AgeAccelPheno                     -0.1091 0.7730  -1.6242   1.4060 0.8877
## DNAmAgeSkinBloodClockAdjAge       -0.3303 0.6485  -1.6013   0.9407 0.6105
## AgeAccelGrim                      -0.3798 0.5342  -1.4268   0.6673 0.4772
## DNAmTLAdjAge                       0.0231 0.0297  -0.0352   0.0814 0.4374
## IEAA                              -0.4115 0.7783  -1.9368   1.1139 0.5970
## EEAA                              -0.1914 0.8294  -1.8171   1.4343 0.8175
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $MEAS6_NO2_SO2
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.0374 0.6678  -1.2714   1.3462 0.9553
## AgeAccelerationResidualHannum      0.6406 0.5799  -0.4959   1.7772 0.2693
## AgeAccelPheno                      0.1016 0.5779  -1.0312   1.2343 0.8605
## DNAmAgeSkinBloodClockAdjAge        0.3942 0.5205  -0.6260   1.4144 0.4488
## AgeAccelGrim                       0.0744 0.4134  -0.7357   0.8846 0.8571
## DNAmTLAdjAge                      -0.0204 0.0264  -0.0721   0.0313 0.4388
## IEAA                              -0.0215 0.5930  -1.1837   1.1407 0.9711
## EEAA                               0.3338 0.6838  -1.0064   1.6740 0.6255
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05

3.5. Clusters based on urinary biomarkers (clusURI5)

The file “LEX_clusURI5.csv” has information on measured urinary biomarkers obtained during each visit. Estimates are available for 5 different prototypes (cluster variables) for a total of 163 subjects and 186 visits. The prototypes are labelled as:

URI5_NAP_1M_2M – a cluster of Naphthalene, 1Methylnaphthalene, and 2Methylnaphthalene
URI5_ACE – Acenaphthene only
URI5_FLU_PHE – Fluoranthene and Phenanthrene_anth
URI5_PYR – Pyrene only
URI5_CHR – Baa_Chrysene only

Summary the exposure estimates:

Other
(N=25)
Smoky
(N=87)
Overall
(N=129)
URI5_NAP_1M_2M
Mean (SD) -0.0895 (1.17) 0.0355 (0.907) 0.0144 (0.961)
Median (IQR) -0.292 (1.25) 0.203 (1.02) 0.0718 (1.21)
Missing 4 (16.0%) 9 (10.3%) 25 (19.4%)
URI5_ACE
Mean (SD) -0.202 (0.757) -0.00423 (1.04) -0.0570 (0.992)
Median (IQR) -0.349 (0.779) -0.00304 (1.43) -0.0905 (1.30)
Missing 4 (16.0%) 9 (10.3%) 25 (19.4%)
URI5_FLU_PHE
Mean (SD) 0.0973 (1.06) -0.0665 (0.934) -0.0462 (0.954)
Median (IQR) -0.145 (1.12) 0.0514 (1.25) 0.0339 (1.26)
Missing 4 (16.0%) 9 (10.3%) 25 (19.4%)
URI5_PYR
Mean (SD) -0.0650 (0.904) 0.0203 (0.906) -0.0183 (0.910)
Median (IQR) -0.0221 (0.698) 0.125 (0.740) 0.0661 (0.750)
Missing 4 (16.0%) 9 (10.3%) 25 (19.4%)
URI5_CHR
Mean (SD) 0.0445 (0.726) -0.000124 (1.10) -0.0113 (1.01)
Median (IQR) -0.178 (0.941) 0.126 (1.02) -0.0395 (0.965)
Missing 4 (16.0%) 9 (10.3%) 25 (19.4%)

Primary analysis

GEE (with confounders)

In this section, we perform the generalized estimating equations (GEE) to evaluate the associations between each cluster within current pollutant exposures and each Epigenetic Age Acceleration with the formula: \[ \begin{aligned} Y = & \beta_0 + \beta_1 * X \\ & + \beta_2 * county + \beta_3 * BMI + \beta_4 * ses + \beta_5 * edu + \epsilon \end{aligned} \] where \(Y\) is one of the epigenetic age accelerations and X is one of the cluster estimates.

Results:

## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."

## The estimated effects:
## $URI5_NAP_1M_2M
##                               coefficient     std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.1207  0.4892  -0.8380   1.0795 0.8051
## AgeAccelerationResidualHannum     -0.5311  0.4726  -1.4574   0.3951 0.2610
## AgeAccelPheno                     -0.0765  0.4506  -0.9597   0.8067 0.8652
## DNAmAgeSkinBloodClockAdjAge       -0.2610  0.3845  -1.0147   0.4927 0.4973
## AgeAccelGrim                       0.4613 11.5825 -22.2404  23.1629 0.9682
## DNAmTLAdjAge                      -0.0190  0.0274  -0.0726   0.0346 0.4875
## IEAA                              -0.0709  0.5298  -1.1093   0.9675 0.8936
## EEAA                              -0.0672  0.5250  -1.0963   0.9618 0.8981
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $URI5_ACE
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.0718 0.4161  -0.8873   0.7437 0.8630
## AgeAccelerationResidualHannum      0.4692 0.3255  -0.1687   1.1071 0.1494
## AgeAccelPheno                      0.8548 0.4681  -0.0628   1.7723 0.0679
## DNAmAgeSkinBloodClockAdjAge       -0.0606 0.3144  -0.6768   0.5557 0.8473
## AgeAccelGrim                      -1.0904 0.3341  -1.7452  -0.4356 0.0011
## DNAmTLAdjAge                      -0.0036 0.0164  -0.0358   0.0285 0.8254
## IEAA                               0.2453 0.4113  -0.5609   1.0515 0.5509
## EEAA                               0.5891 0.4421  -0.2773   1.4556 0.1827
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                    <= 0.01
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $URI5_FLU_PHE
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.2247 0.4454  -0.6483   1.0977 0.6139
## AgeAccelerationResidualHannum      0.2299 0.4475  -0.6472   1.1070 0.6074
## AgeAccelPheno                      0.3113 0.4054  -0.4832   1.1058 0.4425
## DNAmAgeSkinBloodClockAdjAge        0.0430 0.3263  -0.5964   0.6825 0.8950
## AgeAccelGrim                       0.7761 0.7236  -0.6421   2.1943 0.2835
## DNAmTLAdjAge                      -0.0294 0.0419  -0.1114   0.0527 0.4831
## IEAA                               0.1451 0.4563  -0.7491   1.0394 0.7504
## EEAA                               0.5353 0.5835  -0.6083   1.6789 0.3589
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $URI5_PYR
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.0171 0.4598  -0.9183   0.8841 0.9703
## AgeAccelerationResidualHannum      0.4174 0.4215  -0.4088   1.2436 0.3221
## AgeAccelPheno                      1.0257 0.4853   0.0745   1.9770 0.0346
## DNAmAgeSkinBloodClockAdjAge        0.6843 0.4160  -0.1311   1.4998 0.1000
## AgeAccelGrim                       0.6208 0.3417  -0.0490   1.2905 0.0693
## DNAmTLAdjAge                      -0.0339 0.0265  -0.0859   0.0181 0.2018
## IEAA                              -0.0710 0.4712  -0.9945   0.8525 0.8802
## EEAA                               0.6476 0.5407  -0.4122   1.7073 0.2310
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                   <= 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $URI5_CHR
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.0824 0.3638  -0.6306   0.7954 0.8208
## AgeAccelerationResidualHannum      0.1025 0.4291  -0.7384   0.9435 0.8111
## AgeAccelPheno                     -0.0586 0.3702  -0.7843   0.6671 0.8743
## DNAmAgeSkinBloodClockAdjAge        0.0933 0.3141  -0.5222   0.7089 0.7663
## AgeAccelGrim                       0.3337 0.3381  -0.3289   0.9964 0.3236
## DNAmTLAdjAge                      -0.0195 0.2864  -0.5808   0.5419 0.9458
## IEAA                              -0.2279 0.4158  -1.0428   0.5870 0.5836
## EEAA                               0.3170 0.5072  -0.6771   1.3111 0.5320
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05

GEE (Mix, mutual adjust)

In this section, we perform the generalized estimating equations (GEE) to evaluate the associations between each cluster within current pollutant exposures and each Epigenetic Age Acceleration with the formula: \[ \begin{aligned} Y = & \beta_0 + \beta_1 * NAP\_1M\_2M + \beta_2 ACE + \beta_3 FLU\_PHE + \beta_4 PYR + \beta_5 CHR \\ & + \beta_6 * county + \beta_7 * BMI + \beta_8 * ses + \beta_9 * edu + \epsilon \end{aligned} \] where \(Y\) is one of the epigenetic age accelerations.

Results:

## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."

## The estimated effects:
## $URI5_NAP_1M_2M
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.0437 0.5992  -1.1308   1.2182 0.9418
## AgeAccelerationResidualHannum     -1.2381 0.5210  -2.2593  -0.2169 0.0175
## AgeAccelPheno                     -0.4501 0.5919  -1.6102   0.7101 0.4470
## DNAmAgeSkinBloodClockAdjAge       -0.4391 0.5182  -1.4548   0.5765 0.3968
## AgeAccelGrim                       0.0399 2.3489  -4.5640   4.6438 0.9864
## DNAmTLAdjAge                      -0.0189 0.0901  -0.1955   0.1576 0.8336
## IEAA                              -0.3374 0.6410  -1.5937   0.9188 0.5986
## EEAA                              -0.6963 0.6453  -1.9611   0.5685 0.2806
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum   <= 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $URI5_ACE
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.0682 0.4130  -0.8776   0.7413 0.8689
## AgeAccelerationResidualHannum      0.5431 0.3021  -0.0491   1.1353 0.0723
## AgeAccelPheno                      0.8730 0.4527  -0.0143   1.7602 0.0538
## DNAmAgeSkinBloodClockAdjAge       -0.0531 0.2924  -0.6262   0.5199 0.8558
## AgeAccelGrim                       0.3481 1.2322  -2.0671   2.7633 0.7776
## DNAmTLAdjAge                      -0.0326 0.2517  -0.5259   0.4607 0.8969
## IEAA                               0.2118 0.4206  -0.6125   1.0361 0.6145
## EEAA                               0.6167 0.4508  -0.2669   1.5003 0.1714
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $URI5_FLU_PHE
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.2405 0.7019  -1.1353   1.6162 0.7319
## AgeAccelerationResidualHannum      1.1556 0.5839   0.0111   2.3001 0.0478
## AgeAccelPheno                      0.0397 0.6082  -1.1525   1.2318 0.9480
## DNAmAgeSkinBloodClockAdjAge       -0.1676 0.4686  -1.0860   0.7508 0.7206
## AgeAccelGrim                       0.3150 3.3020  -6.1569   6.7869 0.9240
## DNAmTLAdjAge                      -0.0296 0.1850  -0.3921   0.3330 0.8730
## IEAA                               0.6990 0.6426  -0.5604   1.9585 0.2766
## EEAA                               0.6951 0.7493  -0.7736   2.1637 0.3536
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum   <= 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $URI5_PYR
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.1845 0.5705  -1.3028   0.9338 0.7464
## AgeAccelerationResidualHannum      0.1875 0.3734  -0.5444   0.9193 0.6156
## AgeAccelPheno                      1.1701 0.5287   0.1339   2.2063 0.0269
## DNAmAgeSkinBloodClockAdjAge        0.9364 0.4545   0.0456   1.8272 0.0394
## AgeAccelGrim                       0.2992 1.1861  -2.0255   2.6239 0.8008
## DNAmTLAdjAge                       0.0160 0.0677  -0.1167   0.1486 0.8135
## IEAA                              -0.2887 0.6005  -1.4658   0.8883 0.6306
## EEAA                               0.4159 0.5071  -0.5780   1.4099 0.4121
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                   <= 0.05
## DNAmAgeSkinBloodClockAdjAge     <= 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $URI5_CHR
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.0355 0.4677  -0.9522   0.8812 0.9395
## AgeAccelerationResidualHannum      0.0229 0.4457  -0.8506   0.8964 0.9590
## AgeAccelPheno                     -0.0636 0.3610  -0.7710   0.6439 0.8602
## DNAmAgeSkinBloodClockAdjAge        0.1281 0.3592  -0.5759   0.8321 0.7214
## AgeAccelGrim                       0.2868 0.3393  -0.3782   0.9518 0.3979
## DNAmTLAdjAge                      -0.0001 0.0318  -0.0624   0.0622 0.9964
## IEAA                              -0.3663 0.4175  -1.1845   0.4519 0.3802
## EEAA                               0.1912 0.4998  -0.7885   1.1709 0.7021
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05

Sensitivity analyses

GEE (No confounders)

In this section, we perform the generalized estimating equations (GEE) to evaluate the associations between each cluster within current pollutant exposures and each Epigenetic Age Acceleration with the formula: \[ \begin{aligned} Y = & \beta_0 + \beta_1 * X + \epsilon \end{aligned} \] where \(Y\) is one of the epigenetic age accelerations and X is one of the cluster estimates.

Results:

## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."

## The estimated effects:
## $URI5_NAP_1M_2M
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.1532 0.4639  -0.7560   1.0625 0.7412
## AgeAccelerationResidualHannum     -0.4411 0.4313  -1.2864   0.4043 0.3065
## AgeAccelPheno                     -0.1046 0.4350  -0.9572   0.7480 0.8100
## DNAmAgeSkinBloodClockAdjAge       -0.2763 0.3821  -1.0252   0.4725 0.4695
## AgeAccelGrim                       0.6354 0.5447  -0.4322   1.7030 0.2434
## DNAmTLAdjAge                      -0.0216 0.0156  -0.0521   0.0089 0.1650
## IEAA                              -0.0941 0.5013  -1.0767   0.8885 0.8511
## EEAA                              -0.1278 0.5175  -1.1422   0.8865 0.8049
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $URI5_ACE
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.2304 0.5036  -1.2174   0.7566 0.6473
## AgeAccelerationResidualHannum      0.4233 0.3107  -0.1857   1.0324 0.1731
## AgeAccelPheno                      0.6801 0.4330  -0.1685   1.5287 0.1162
## DNAmAgeSkinBloodClockAdjAge       -0.0808 0.3108  -0.6900   0.5284 0.7949
## AgeAccelGrim                       0.7049 0.5222  -0.3187   1.7285 0.1771
## DNAmTLAdjAge                      -0.0117 0.0111  -0.0336   0.0101 0.2928
## IEAA                               0.0695 0.4100  -0.7340   0.8731 0.8653
## EEAA                               0.4882 0.4146  -0.3244   1.3009 0.2389
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $URI5_FLU_PHE
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.1892 0.4185  -1.0094   0.6309 0.6511
## AgeAccelerationResidualHannum      0.2082 0.4149  -0.6049   1.0213 0.6158
## AgeAccelPheno                      0.3825 0.4086  -0.4184   1.1833 0.3492
## DNAmAgeSkinBloodClockAdjAge        0.0187 0.3207  -0.6098   0.6472 0.9535
## AgeAccelGrim                       0.6827 0.4408  -0.1812   1.5466 0.1214
## DNAmTLAdjAge                      -0.0397 0.0138  -0.0669  -0.0126 0.0041
## IEAA                               0.0819 0.4419  -0.7842   0.9480 0.8530
## EEAA                               0.4182 0.5515  -0.6627   1.4992 0.4482
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                    <= 0.01
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $URI5_PYR
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.7635 0.5926  -1.9250   0.3981 0.1977
## AgeAccelerationResidualHannum      0.3412 0.3616  -0.3675   1.0498 0.3454
## AgeAccelPheno                      0.8858 0.4224   0.0579   1.7136 0.0360
## DNAmAgeSkinBloodClockAdjAge        0.5683 0.3935  -0.2030   1.3397 0.1487
## AgeAccelGrim                       0.4230 0.2848  -0.1352   0.9812 0.1375
## DNAmTLAdjAge                      -0.0242 0.0176  -0.0587   0.0103 0.1689
## IEAA                              -0.3345 0.4314  -1.1800   0.5109 0.4380
## EEAA                               0.3930 0.4695  -0.5272   1.3132 0.4025
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                   <= 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $URI5_CHR
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.0109 0.3471  -0.6913   0.6695 0.9748
## AgeAccelerationResidualHannum      0.0720 0.3938  -0.6998   0.8439 0.8548
## AgeAccelPheno                     -0.0272 0.3774  -0.7670   0.7126 0.9425
## DNAmAgeSkinBloodClockAdjAge        0.0536 0.2869  -0.5087   0.6159 0.8518
## AgeAccelGrim                       0.4199 0.2632  -0.0960   0.9358 0.1106
## DNAmTLAdjAge                      -0.0256 0.0202  -0.0653   0.0140 0.2046
## IEAA                              -0.2227 0.3728  -0.9534   0.5079 0.5502
## EEAA                               0.2021 0.4913  -0.7610   1.1651 0.6809
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05

GEE (No confounders, mutual adjust)

In this section, we perform the generalized estimating equations (GEE) to evaluate the associations between each cluster within current pollutant exposures and each Epigenetic Age Acceleration with the formula: \[ \begin{aligned} Y = & \beta_0 + \beta_1 * NAP\_1M\_2M + \beta_2 ACE + \beta_3 FLU\_PHE + \beta_4 PYR + \beta_5 CHR \\ & + \epsilon \end{aligned} \] where \(Y\) is one of the epigenetic age accelerations.

Results:

## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."
## [1] "Fitting with 104 observations."

## The estimated effects:
## $URI5_NAP_1M_2M
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.5799 0.5186  -0.4366   1.5964 0.2635
## AgeAccelerationResidualHannum     -1.3080 0.5109  -2.3094  -0.3066 0.0105
## AgeAccelPheno                     -0.6566 0.5159  -1.6677   0.3545 0.2031
## DNAmAgeSkinBloodClockAdjAge       -0.4663 0.4402  -1.3290   0.3965 0.2895
## AgeAccelGrim                       0.0280 0.5074  -0.9665   1.0225 0.9560
## DNAmTLAdjAge                       0.0089 0.0249  -0.0398   0.0576 0.7212
## IEAA                              -0.2678 0.5757  -1.3963   0.8606 0.6418
## EEAA                              -0.8372 0.6296  -2.0712   0.3969 0.1836
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum   <= 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $URI5_ACE
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.1807 0.4395  -1.0421   0.6808 0.6810
## AgeAccelerationResidualHannum      0.5468 0.2993  -0.0398   1.1333 0.0677
## AgeAccelPheno                      0.6156 0.4330  -0.2331   1.4643 0.1551
## DNAmAgeSkinBloodClockAdjAge       -0.0957 0.2955  -0.6748   0.4834 0.7460
## AgeAccelGrim                       0.4820 0.4113  -0.3241   1.2880 0.2412
## DNAmTLAdjAge                      -0.0185 0.0173  -0.0524   0.0154 0.2838
## IEAA                               0.0973 0.4108  -0.7079   0.9025 0.8128
## EEAA                               0.5458 0.4209  -0.2792   1.3707 0.1947
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $URI5_FLU_PHE
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.5462 0.7525  -2.0210   0.9287 0.4680
## AgeAccelerationResidualHannum      1.2976 0.5678   0.1848   2.4104 0.0223
## AgeAccelPheno                      0.5314 0.6116  -0.6672   1.7301 0.3848
## DNAmAgeSkinBloodClockAdjAge       -0.1065 0.3901  -0.8711   0.6580 0.7848
## AgeAccelGrim                       0.3521 0.6006  -0.8251   1.5293 0.5577
## DNAmTLAdjAge                      -0.0596 0.0404  -0.1387   0.0195 0.1399
## IEAA                               0.7401 0.6230  -0.4810   1.9612 0.2348
## EEAA                               0.9160 0.7319  -0.5184   2.3505 0.2107
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum   <= 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $URI5_PYR
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual           -0.4994 0.5663  -1.6094   0.6106 0.3779
## AgeAccelerationResidualHannum      0.0560 0.3586  -0.6468   0.7588 0.8758
## AgeAccelPheno                      0.8131 0.4791  -0.1258   1.7521 0.0896
## DNAmAgeSkinBloodClockAdjAge        0.8124 0.4260  -0.0227   1.6474 0.0565
## AgeAccelGrim                       0.0904 0.3204  -0.5376   0.7183 0.7779
## DNAmTLAdjAge                       0.0110 0.0990  -0.1831   0.2051 0.9117
## IEAA                              -0.5912 0.5604  -1.6897   0.5072 0.2914
## EEAA                               0.0925 0.4799  -0.8481   1.0332 0.8471
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05
## 
## $URI5_CHR
##                               coefficient    std ci_lower ci_upper  p_val
## AgeAccelerationResidual            0.1974 0.6600  -1.0962   1.4910 0.7648
## AgeAccelerationResidualHannum     -0.0386 0.4389  -0.8989   0.8217 0.9299
## AgeAccelPheno                     -0.2237 0.3923  -0.9926   0.5451 0.5685
## DNAmAgeSkinBloodClockAdjAge        0.0808 0.3647  -0.6341   0.7957 0.8247
## AgeAccelGrim                       0.2639 0.2049  -0.1377   0.6654 0.1977
## DNAmTLAdjAge                       0.0081 0.0601  -0.1096   0.1259 0.8923
## IEAA                              -0.3579 0.3994  -1.1407   0.4249 0.3702
## EEAA                               0.0574 0.5048  -0.9321   1.0469 0.9094
##                               sig_level
## AgeAccelerationResidual          > 0.05
## AgeAccelerationResidualHannum    > 0.05
## AgeAccelPheno                    > 0.05
## DNAmAgeSkinBloodClockAdjAge      > 0.05
## AgeAccelGrim                     > 0.05
## DNAmTLAdjAge                     > 0.05
## IEAA                             > 0.05
## EEAA                             > 0.05

4.1. Current exposure to 5MC

Summary the exposure estimates:

Other
(N=25)
Smoky
(N=87)
Overall
(N=129)
cur_5mc
Mean (SD) 4.91 (2.83) 9.09 (4.38) 8.15 (4.23)
Median (IQR) 5.05 (4.84) 9.46 (4.50) 8.26 (4.48)
Missing 2 (8.0%) 1 (1.1%) 3 (2.3%)

Primary analysis

GEE (with confounders)

In the following section, we performed generalized estimating equations (GEE) with equation \[ \begin{aligned} Y = & \beta_0 + \beta_1 *cur\_5mc\\ & + \beta_2 * county + \beta_3 * BMI + \beta_4 * ses + \beta_5 * edu + \epsilon \end{aligned} \] where \(Y\) is one of the epigenetic age accelerations.

Results:

## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."

## [1] " Result data: "
##                                coefficient                 std    ci_lower
## AgeAccelerationResidual        0.043405227   0.115493287924362 -0.18296162
## AgeAccelerationResidualHannum -0.027158185  0.0999991181792323 -0.22315646
## AgeAccelPheno                  0.118926749   0.100656276642595 -0.07835955
## DNAmAgeSkinBloodClockAdjAge    0.116943084  0.0716231975184864 -0.02343838
## AgeAccelGrim                   0.148955554  0.0506687424790981  0.04964482
## DNAmTLAdjAge                  -0.004557601 0.00327977322802548 -0.01098596
## IEAA                           0.020150560   0.123949043708331 -0.22278957
## EEAA                          -0.042628589   0.132789328425354 -0.30289567
##                                  ci_upper               p_val sig_level
## AgeAccelerationResidual       0.269772072   0.707047242657413    > 0.05
## AgeAccelerationResidualHannum 0.168840087   0.785941715190563    > 0.05
## AgeAccelPheno                 0.316213051   0.237398797561661    > 0.05
## DNAmAgeSkinBloodClockAdjAge   0.257324551   0.102520682085509    > 0.05
## AgeAccelGrim                  0.248266290 0.00328432839999115   <= 0.01
## DNAmTLAdjAge                  0.001870755   0.164647803635041    > 0.05
## IEAA                          0.263090685   0.870855969945509    > 0.05
## EEAA                          0.217638494   0.748192043476084    > 0.05
##                                         EAAs
## AgeAccelerationResidual          Horvath EAA
## AgeAccelerationResidualHannum     Hannum EAA
## AgeAccelPheno                   PhenoAge EAA
## DNAmAgeSkinBloodClockAdjAge   Skin&Blood EAA
## AgeAccelGrim                     GrimAge EAA
## DNAmTLAdjAge                          DNAmTL
## IEAA                                    IEAA
## EEAA                                    EEAA

Sensitivity analysis

GEE (no confounders)

In the following section, we performed generalized estimating equations (GEE) with equation \[ \begin{aligned} Y = & \beta_0 + \beta_1 *cur\_5mc + \epsilon \end{aligned} \] where \(Y\) is one of the epigenetic age accelerations.

Results:

## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."

## [1] " Result data: "
##                                coefficient                 std    ci_lower
## AgeAccelerationResidual        0.044863339   0.113864633110002 -0.17831134
## AgeAccelerationResidualHannum -0.017041115  0.0978064100987568 -0.20874168
## AgeAccelPheno                  0.107159703   0.100283750609095 -0.08939645
## DNAmAgeSkinBloodClockAdjAge    0.106144306  0.0713739765678327 -0.03374869
## AgeAccelGrim                   0.140523649  0.0550039747044841  0.03271586
## DNAmTLAdjAge                  -0.004200799 0.00335993883966329 -0.01078628
## IEAA                           0.016148695   0.121516907890369 -0.22202444
## EEAA                          -0.025686042   0.127591566498255 -0.27576551
##                                  ci_upper              p_val sig_level
## AgeAccelerationResidual       0.268038020  0.693576669249562    > 0.05
## AgeAccelerationResidualHannum 0.174659449   0.86168226954879    > 0.05
## AgeAccelPheno                 0.303715854  0.285265741749724    > 0.05
## DNAmAgeSkinBloodClockAdjAge   0.246037300  0.136973360441059    > 0.05
## AgeAccelGrim                  0.248331440 0.0106251631971735   <= 0.05
## DNAmTLAdjAge                  0.002384681  0.211204364462331    > 0.05
## IEAA                          0.254321835  0.894278337455743    > 0.05
## EEAA                          0.224393428  0.840452605508899    > 0.05
##                                         EAAs
## AgeAccelerationResidual          Horvath EAA
## AgeAccelerationResidualHannum     Hannum EAA
## AgeAccelPheno                   PhenoAge EAA
## DNAmAgeSkinBloodClockAdjAge   Skin&Blood EAA
## AgeAccelGrim                     GrimAge EAA
## DNAmTLAdjAge                          DNAmTL
## IEAA                                    IEAA
## EEAA                                    EEAA

4.2. Childhood exposure to 5MC

Summary the exposure estimates:

Other
(N=25)
Smoky
(N=87)
Overall
(N=129)
bir_5mc
Mean (SD) 4.39 (2.96) 5.57 (2.85) 5.22 (2.82)
Median (IQR) 3.70 (5.23) 4.83 (5.17) 4.75 (5.34)
Missing 2 (8.0%) 1 (1.1%) 3 (2.3%)

Primary analysis

GEE (with confounders)

In the following section, we performed generalized estimating equations (GEE) with equation \[ \begin{aligned} Y = & \beta_0 + \beta_1 *childhood\_5mc\\ & + \beta_2 * county + \beta_3 * BMI + \beta_4 * ses + \beta_5 * edu + \epsilon \end{aligned} \] where \(Y\) is one of the epigenetic age accelerations.

Results:

## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."

## [1] " Result data: "
##                                coefficient                 std     ci_lower
## AgeAccelerationResidual        0.013581238     0.1525495208842 -0.285415823
## AgeAccelerationResidualHannum  0.135320612   0.143152618792748 -0.145258521
## AgeAccelPheno                  0.288191817   0.150828508622891 -0.007432059
## DNAmAgeSkinBloodClockAdjAge    0.156895355   0.112196416684544 -0.063009621
## AgeAccelGrim                   0.299554330  0.0856477119470605  0.131684815
## DNAmTLAdjAge                  -0.001670684 0.00638501299772504 -0.014185309
## IEAA                          -0.134530357    0.14459026100462 -0.417927269
## EEAA                           0.222801828   0.182782972150885 -0.135452798
##                                 ci_upper                p_val sig_level
## AgeAccelerationResidual       0.31257830    0.929059351419451    > 0.05
## AgeAccelerationResidualHannum 0.41589974    0.344511294913712    > 0.05
## AgeAccelPheno                 0.58381569    0.056039917225708    > 0.05
## DNAmAgeSkinBloodClockAdjAge   0.37680033    0.161993287747863    > 0.05
## AgeAccelGrim                  0.46742385 0.000469610751128058  <= 0.001
## DNAmTLAdjAge                  0.01084394    0.793585821402502    > 0.05
## IEAA                          0.14886655    0.352151209489498    > 0.05
## EEAA                          0.58105645    0.222866236215159    > 0.05
##                                         EAAs
## AgeAccelerationResidual          Horvath EAA
## AgeAccelerationResidualHannum     Hannum EAA
## AgeAccelPheno                   PhenoAge EAA
## DNAmAgeSkinBloodClockAdjAge   Skin&Blood EAA
## AgeAccelGrim                     GrimAge EAA
## DNAmTLAdjAge                          DNAmTL
## IEAA                                    IEAA
## EEAA                                    EEAA

Sensitivity analysis

GEE (no confounders)

In the following section, we performed generalized estimating equations (GEE) with equation \[ \begin{aligned} Y = & \beta_0 + \beta_1 *childhood\_5mc + \epsilon \end{aligned} \] where \(Y\) is one of the epigenetic age accelerations.

Results:

## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."

## [1] " Result data: "
##                                coefficient                 std    ci_lower
## AgeAccelerationResidual        0.044863339   0.113864633110002 -0.17831134
## AgeAccelerationResidualHannum -0.017041115  0.0978064100987568 -0.20874168
## AgeAccelPheno                  0.107159703   0.100283750609095 -0.08939645
## DNAmAgeSkinBloodClockAdjAge    0.106144306  0.0713739765678327 -0.03374869
## AgeAccelGrim                   0.140523649  0.0550039747044841  0.03271586
## DNAmTLAdjAge                  -0.004200799 0.00335993883966329 -0.01078628
## IEAA                           0.016148695   0.121516907890369 -0.22202444
## EEAA                          -0.025686042   0.127591566498255 -0.27576551
##                                  ci_upper              p_val sig_level
## AgeAccelerationResidual       0.268038020  0.693576669249562    > 0.05
## AgeAccelerationResidualHannum 0.174659449   0.86168226954879    > 0.05
## AgeAccelPheno                 0.303715854  0.285265741749724    > 0.05
## DNAmAgeSkinBloodClockAdjAge   0.246037300  0.136973360441059    > 0.05
## AgeAccelGrim                  0.248331440 0.0106251631971735   <= 0.05
## DNAmTLAdjAge                  0.002384681  0.211204364462331    > 0.05
## IEAA                          0.254321835  0.894278337455743    > 0.05
## EEAA                          0.224393428  0.840452605508899    > 0.05
##                                         EAAs
## AgeAccelerationResidual          Horvath EAA
## AgeAccelerationResidualHannum     Hannum EAA
## AgeAccelPheno                   PhenoAge EAA
## DNAmAgeSkinBloodClockAdjAge   Skin&Blood EAA
## AgeAccelGrim                     GrimAge EAA
## DNAmTLAdjAge                          DNAmTL
## IEAA                                    IEAA
## EEAA                                    EEAA

4.3. Cumulative exposure to 5MC

Summary the exposure estimates:

Other
(N=25)
Smoky
(N=87)
Overall
(N=129)
cum_5mc
Mean (SD) 220 (164) 292 (150) 275 (150)
Median (IQR) 133 (214) 270 (209) 257 (209)
Missing 2 (8.0%) 1 (1.1%) 3 (2.3%)

Primary analysis

GEE (with confounders)

In the following section, we performed generalized estimating equations (GEE) with equation \[ \begin{aligned} Y = & \beta_0 + \beta_1 *cum\_5mc\\ & + \beta_2 * county + \beta_3 * BMI + \beta_4 * ses + \beta_5 * edu + \epsilon \end{aligned} \] where \(Y\) is one of the epigenetic age accelerations.

Results:

## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."

## [1] " Result data: "
##                                 coefficient                  std      ci_lower
## AgeAccelerationResidual        0.0011297683  0.00321754110538496 -0.0051766123
## AgeAccelerationResidualHannum  0.0024297203  0.00286859328247939 -0.0031927225
## AgeAccelPheno                  0.0046561822  0.00315660422742595 -0.0015307621
## DNAmAgeSkinBloodClockAdjAge    0.0022230277  0.00243998088414274 -0.0025593349
## AgeAccelGrim                   0.0058800703  0.00161826592950822  0.0027082691
## DNAmTLAdjAge                  -0.0001174706 0.000128468642577699 -0.0003692691
## IEAA                          -0.0007651314  0.00302849757225974 -0.0067009866
## EEAA                           0.0042085613  0.00367291833078406 -0.0029903586
##                                   ci_upper                p_val sig_level
## AgeAccelerationResidual       0.0074361488    0.725492440526316    > 0.05
## AgeAccelerationResidualHannum 0.0080521632    0.396990881252127    > 0.05
## AgeAccelPheno                 0.0108431264    0.140196283843566    > 0.05
## DNAmAgeSkinBloodClockAdjAge   0.0070053902    0.362251089952007    > 0.05
## AgeAccelGrim                  0.0090518716 0.000279534738611642  <= 0.001
## DNAmTLAdjAge                  0.0001343279    0.360511350051069    > 0.05
## IEAA                          0.0051707239      0.8005434220148    > 0.05
## EEAA                          0.0114074812    0.251863102495362    > 0.05
##                                         EAAs
## AgeAccelerationResidual          Horvath EAA
## AgeAccelerationResidualHannum     Hannum EAA
## AgeAccelPheno                   PhenoAge EAA
## DNAmAgeSkinBloodClockAdjAge   Skin&Blood EAA
## AgeAccelGrim                     GrimAge EAA
## DNAmTLAdjAge                          DNAmTL
## IEAA                                    IEAA
## EEAA                                    EEAA

Sensitivity analysis

GEE (no confounders)

In the following section, we performed generalized estimating equations (GEE) with equation \[ \begin{aligned} Y = & \beta_0 + \beta_1 *cum\_5mc + \epsilon \end{aligned} \] where \(Y\) is one of the epigenetic age accelerations.

Results:

## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."
## [1] "Fitting with 126 observations."

## [1] " Result data: "
##                                 coefficient                  std      ci_lower
## AgeAccelerationResidual       -0.0009917356   0.0027245425973913 -0.0063318390
## AgeAccelerationResidualHannum  0.0024968640  0.00247936234502612 -0.0023626862
## AgeAccelPheno                  0.0047965293  0.00266935100058998 -0.0004353987
## DNAmAgeSkinBloodClockAdjAge    0.0013096169  0.00207570564676486 -0.0027587661
## AgeAccelGrim                   0.0047733361  0.00163901122252633  0.0015608741
## DNAmTLAdjAge                  -0.0001203660 0.000108228672285064 -0.0003324941
## IEAA                          -0.0015487572  0.00257420977692438 -0.0065942084
## EEAA                           0.0035090514  0.00318009041422209 -0.0027239258
##                                    ci_upper               p_val sig_level
## AgeAccelerationResidual       0.00434836794   0.715857447596787    > 0.05
## AgeAccelerationResidualHannum 0.00735641417   0.313906458923568    > 0.05
## AgeAccelPheno                 0.01002845722  0.0723531358161104    > 0.05
## DNAmAgeSkinBloodClockAdjAge   0.00537799999   0.528088827964163    > 0.05
## AgeAccelGrim                  0.00798579808 0.00358747245035784   <= 0.01
## DNAmTLAdjAge                  0.00009176225   0.266075912628183    > 0.05
## IEAA                          0.00349669395   0.547411302915121    > 0.05
## EEAA                          0.00974202860   0.269834439221523    > 0.05
##                                         EAAs
## AgeAccelerationResidual          Horvath EAA
## AgeAccelerationResidualHannum     Hannum EAA
## AgeAccelPheno                   PhenoAge EAA
## DNAmAgeSkinBloodClockAdjAge   Skin&Blood EAA
## AgeAccelGrim                     GrimAge EAA
## DNAmTLAdjAge                          DNAmTL
## IEAA                                    IEAA
## EEAA                                    EEAA

4.4. 5MC (Current, Childhood, Cumulative)